Seminar V

Steroid vs peptide hormones

- Three general classes of hormones exist
1. Proteins and polypeptides -> hormones secreted by anterior puitary and posterior
puitary gland, the pancreas (insulin and glucagon), the parathyroid gland
(parathyroid hormone)
2. Steroids-> secreted by adrenal cortex (cortisol and aldosterone), ovaries and
placenta (estrogen, progesterone) and testis (testosterone)
3. Derivatives of the amino acid tyrosine-> secreted by thyroid (thyroxine,
triiodothyronine) and adrenal medulla (epinephrine, norepinephrine)
Peptide hormones
- Polypeptide and protein hormones are stored in secretory vesicles until needed
- Most of the hormones in the body are polypeptides and proteins-> range in size from small
peptide with 3 aa to proteins with almost 200 aa
- In general polypeptides with 100 or more are called proteins and those with fewer than
100 are called peptides
- Proteins and peptide hormones are synthesized on the rough end of the endoplasmic
reticulum of different endocrine cells in the same fashion as many their proteins
- They are usually synthesized first as larger proteins that are not biologically active (pre-
prohormones) and are cleaved to form smaller prohormones in the endoplasmic reticulum
- These prohormones are then transferred to the Golgi apparatus for packaging into
secretory vesicles -> in this process enzymes in the vesicles cleave the prohormones to
produce smaller, biologically active hormones and inactive fragments
- The vesicles are stored within the cytoplasm and many are bound to the cell membrane
until their secretion is needed
- Secretion of hormone (as well inactive fragments) occurs when the secretory vesicles fuse
with the cell membrane and the granular contents are extruded into interstitial fluid or
directly into the blood stream by exocytosis
- In many cases the stimulus for endocytosis is increased cytosolic calcium concentration
caused by depolarization of plasma membrane
- In other instances, stimulation of an endocrine cell surface receptor causes increased cyclic
adenosine monophosphate cAMP and subsequently activation of protein kinases that
initiate secretion of hormone
- The peptide hormones are water soluble, allowing them to enter the circulatory system
easily where they are carried to their target tissues
Steroid hormones
- Steroid hormones are not usually synthesized from cholesterol and are nor stored
- The chemical structure of steroid hormones is similar to that of cholesterol and in most
instances hormones are synthesized from cholesterol
- They are lipid soluble and consist of cyclohexyl rings and one cyclopentyl ring combined
into a single structure
- Although there is usually very little hormone storage in steroid producing endocrine cells,
large stores of cholesterol enters in cytoplasm vacuoles can be rapidly mobilized for steroid
synthesis after a stimulus
- Much of the cholesterol in steroid producing cells comes from plasma but there is also de
novo synthesis of cholesterol in steroid producing cells
 - Because the steroids are highly lipid soluble once they are synthesized they can simply
diffuse across the cell membrane and enter the interstitial fluid and then the blood
Amide hormones
- They are derived from tyrosine and they are two groups-> thyroid and the adrenal
medullary hormones which are formed by the actions of enzymes in the cytoplasmic
compartments of glandular cells
- The thyroid hormones are formed by the actions of enzymes in the cytoplasmic
compartments of the glandular cells
- The thyroid hormones are synthesized and stored in large follicles within the thyroid glans
- Hormone secretion occurs when the amines are split from thyroglobulin and the free
hormones are then released into the blood stream
- After entering the blood most of the thyroid hormones combine with plasma proteins
especially, thyroxine-binding globulin which slowly releases the hormones to the target
tissues
- Epinephrine and norepinephrine are formed in adrenal medulla which normally secretes
about four times more epinephrine than norepinephrine
- Catecholamines are taken up into preformed vesicles and stored until secrete
- Similar to the protein hormones stored in secretory granules, catecholamines are also
released from adrenal medullary cells by exocytosis
- Once the catecholamines enter the circulation they can exists in the plasma in free form or
in conjugation with other substances
Transport of hormones in the blood
Water soluble hormones (peptides and catecholamines)
- They are dissolved in the plasma and transported from their sites of synthesis to the target
tissues, where they diffuse out of capillaries into the interstitial fluid and ultimately to
target cells
Steroid and thyroid hormones
- They circulate in blood while being mainly bound to plasma proteins
- Usually less than 10% of steroid or thyroid hormones in the plasma exists in free solution->
e.g. more than 99% of the thyroxine in the bound to plasma proteins
- Protein bound hormones cannot easily diffuse across capillaries and gain access to their
target cells and are therefore biologically inactive until they dissociate from plasma
proteins
- The relatively large amounts of hormones bound to proteins serve as reservoirs,
replenishing the concentration of free hormones when they are bound to target receptors
or lost from the circulation
- Binding of hormones to plasma proteins greatly slows their clearance (rate of removal of
the hormone from the blood) from the plasma
Hormone receptors and activation
- First step is to bind to specific receptors at target cell
- Cells that lack receptors for hormones do not respond
- Receptors for some hormones are located on the target cell membrane whereas other
hormone receptors are located in the cytoplasm or nucleus
- When the hormone combined with its receptors this action usually initiates a cascade of
reactions in the cell with each stage becoming more powerfully activated so that even
small concentrations of the hormone can have a large effect
 - Hormone receptors are large proteins and each cell that is to be stimulated usually has
some 2000 to 100 000 receptor-> each receptors is usually high specific for a single
hormone which determine the type of hormone that will act on a particular tissue
- The target tissue that are affected by a hormone are those that contain its specific
receptors
- Locations for different types of hormone receptors
o In or on the surface of cell membrane -> protein, peptide and catecholamine
hormones
o In the cell cytoplasm-> primary receptors for steroid hormones
o In cell nucleus -> thyroid hormones
Feedback control of hormone secretion
- Although plasma concentration of many hormones fluctuate in response various stimuli
that occur all hormones are studied appear to be closely controlled
- In most instances this control exerted through negative feedback mechanisms that ensures
a proper level of hormone activity at the target tissue
- After a stimulus causes release of the hormone, conditions or products resulting from the
action of the hormone tend to suppress its further release -> the hormone (or one of its
product) has negative feedback effect to prevent over secretion of the hormone or
overactivity at the target tissue
- The controlled variable is sometimes not the secretory rate of the hormone but the degree
of activity of the target tissue-> only when the target tissue activity rises to an appropriate
level will feedback signals to the endocrine glans becoming powerful enough to slow
further secretion of the hormone
- Feedback regulation of hormones can occur at all levels, including gene transcription and
translation step involved in the synthesis of hormones and steps involved in processing
hormones or releasing stored hormones
- Positive feedback occurs when the biological action of the hormone causes additional
secretion of the hormone
- One example is the surge of luteinizing hormone (LH) that occurs as a result of the
stimulatory effect of estrogen on the anterior puitary before ovulation
- The secreted LH then accts on the ovaries to stimulate additional secretion of estrogen
which in turn causes more secretion of LH
- Eventually LH reaches an appropriate concentration and typical negative feedback control
of hormone secretion is then exerted
- Superimposed on the negative and positive feedback control of hormone secretion are
periodic variations in hormone release that are influenced by seasonal changes, various
stages of development and aging, the diurnal (daily) cycle and sleep
- For example the secretion of growth hormone is markedly increased during the early
period of sleep but is reduced during the later stages of sleep
- In many cases these cyclical variations in hormone secretion are due to changes in activity
of neural pathway involved in controlling hormone release
Male sex hormones
- A major share of control of sexual functions in both male and female begins with secretion
of gonadotropin-releasing hormone (GnRH) by the hypothalamus -> this hormone in turn
stimulates the anterior puitary gland to secrete two other hormones
o Luteinizing hormone (LH)
o Follicle stimulating hormone (FSH)
 - In turn LH is the primary stimulus for the secretion of testosterone by testes and FSH
mainly stimulates spermatogenesis
GnRH and its effect in increasing the secretion of luteinizing hormone and follicle stimulating
hormone
- GnRH is a 10 aa peptide secreted by neurons whose cell bodies are located in the arcuate
nuclei of the hypothalamus
- The ending of these neurons terminate mainly in the median eminence of the
hypothalamus where they release GnRH into the hypothalamic-hypophysial portal vascular
system
- The GnRH is then transported to the anterior puitary gland in the hypophysial portal blood
and stimulates the release of the two gonadotropins -> LH and FSH
- GnRH is secreted a few minutes at a time once every 1-3h
- The intensity of this hormone’s stimulus is determined in two ways
o By the frequency of these cycles of secretion
o By the quantity of GnRH released with each cycle
- The secretion of LH by the anterior puitary gland is also cyclical, with LH following fairly
faithfully the pulsatile release of GnRH
- FSH secretion increases and decreases only slightly with each fluctuation of GnRH secretion
-> it changes more slowly over a period of many hours in response to longer-term changes
in GnRH
- Because of the much closer relation between GnRH and LH secretion, GnRH is also widely
known as LH- releasing hormone
LH and FSH
- Both gonadotropic hormones are secreted by the same cells called gonadotrophs in the
anterior puitary glans
- In the absence of GnRH secretion from the hypothalamus the gonadotrophs in the puitary
gland secrete almost no LH or FSH
- LH and FSH are glycoproteins -> they exert their effects on target tissue in testes mainly by
activating the cAMP second messenger system which in turns activates specific enzyme
systems in the respective target cells
Testosterone
- Testes secrete several male sex hormones called androgens-> testosterone,
dihydrotestosterone and androstenedione
- Testosterone-> much abundant because is the primary testicular hormone
- It’s formed by the interstitial cells of Leydig which lie in the interstices btw seminiferous
tubules
- Leydig cells are almost nonexistent in childhood when the testes secrete almost no
testosterone but they are numerous in newborn male infant for the first few months of life
and in adult after puberty
Function
- It’s responsible for the distinguishing characteristics of male body
- Even during fetal life the teste are stimulated by chorionic gonadotropin from the placenta
to produce moderate quantities of testosterone throughout the entire period of fetal
development and for 10 weeks after birth (no testosterone is produced during childhood
until 10-13 y)
- Testosterone production then increases rapidly under the stimulus of anterior puitary
gonadotropic hormones at the onset of puberty and lasts throughout most of the life
1. Embryonic development
 - Testosterone begins to be elaborated by the male fetal testes about the 7 th week of
embryonic life -> major functional differences between the female and the male sex
chromones is that the male chromosome has the sex determining region Y (SRY) gene that
encodes a protein called the testis determining factor (SRY protein)
- SRY protein initiates a cascade of gene activations that cause the genital ridge cells to
differentiate into cells that secrete testosterone and eventually become the testis, whereas
in female chromosome causes this ridge to differentiate into cells that secrete estrogens
- Testosterone secreted first by genital ridges and later by fetal testes is responsible for
development of male body characteristic including formation of penis and scrotum,
prostate gland, seminal vesicles and male genital ducts while at the same time suppressing
the formation of female genital organs
2. Descent of testis
- Testis usually descend into the scrotum during the last 2/3 months of gestation when the
testis begin secreting reasonable quantities of testosterone
- If male child is born with undescended but normal testes administration of testosterone
usually causes the testes to descend in the usual manner if inguinal canals are large enough
to allow the testes to pass
3. Development of primary and secondary sexual characteristics
- Effects on distribution of body hair-> testosterone causes growth of air over the pubis,
upward along linea alba and sometimes to the umbilicus and above, on the face, chest and
less often on the regions of the body such as the back (it can cause hair on other portions
to become more prolific)
- Male pattern baldness-> testosterone decreases the growth of hair on the top pf the head
(a man w/ dysfunctional testes doesn’t become bald).
o Many men never become bald because baldness is result of two factors
 Genetic background
 Large quantities of androgenic hormones
o When a long sustains androgenic tumor develops in a woman who has the
appropriate genetic background she becomes bald in the same manner as man
- Effect on voice -> it causes hypertrophy of the laryngeal mucosa and enlargement of larynx
- Increases thickness of the skin and contribute to acne -> testosterone increases the
thickness of the skin over the entire body and increases the rate of secretion of all body’s
sebaceous glans
o Important is over secretion by sebaceous glans of the face which can results in acne
o After several years of testosterone secretion the skin normally adapts to the
testosterone in a way that allows t to overcome the acne
- Increases protein formation and muscle development -> the increase in muscle mass is
associated with increased protein in non-muscle parts of the body as well
o Many changes in the skin are due to deposit of protein in the skin and the changes
in the voice result partly from this protein anabolic function of testosterone
o They improve muscle strength and vigor -> synthetic androgens used by athletes
- Increases bone matrix and causes calcium retention -> the bones grow considerably thicker
and deposit additional calcium salts
o The increase of bone matrix is believed to result from the general protein anabolic
function of testosterone plus deposit of calcium salts in response to the increased
protein
 o Testosterone has effect on the pelvis-> narrow the pelvic outlet, lengthen in, causes
a funnel-like shape instead of ovoid shape of female pelvis and greatly increase the
strength of the entire pelvis
o When great quantities of testosterone are secreted abnormally in the still growing
child the rate of bone growth increases markedly causing a spurt in total body
height
- Increases basal metabolic rate-> indirect effect of testosterone on protein anabolism with
increased quantity of proteins increasing activity of all cells
- Increases RBC-> men have 700 000 more rbc per cubic millimeter than average women
o Testosterone does not appear to directly increase erythropoietin levels or have a
direct effect on rbc production
o May be at least partly indirect because of the increased metabolic rate
- Effect on electrolyte and water balance -> many steroid hormones can increase
reabsorption of sodium in the distal tubules of the kidneys
o Testosterone has such an effect but only to a minor degree in comparison with
adrenal mineralocorticoids
o After puberty the blood and extracellular fluid volumes of the male in relation to
body weight increases as much as 5-10%
Regulation of testosterone producing by luteinizing hormone
- Inhibition of anterior puitary secretion of LH and FSH by testosterone-negative feedback
control of testosterone secretion
- The testosterone secreted by the testes in response to LH has the reciprocal effect of
inhibiting anterior puitary secretion of LH
- Most of this inhibition results from a direct effect of testosterone on the hypothalamus to
decrease the secretion of GnRH -> this effect in turn causes a corresponding decrease in
secretion of both LH and FSH by the anterior puitary and the decrease in LH reduces the
secretion of testosterone by the testis
- Whenever the secretion of testosterone becomes too great this automatic negative
feedback effect operating through the hypothalamus and anterior puitary glans reduces
the testosterone secretion back toward the desired operating level
- Too little testosterone allows the hypothalamus to secrete large amount of GnRH with of a
corresponding increase in anterior puitary gland LH and FSH secretion and consequent
increase in testosterone secretion in testis
Spermatogenesis by FSH and testosterone
- FSH binds with specific FSH receptors attached to Sertoli cells in seminiferous tubules
which causes Sertoli cells to grow and secrete various spermatogenic substance
- Testosterone diffusing into the seminiferous tubules from the Leydig cells in the interstitial
space has a strong tropic effect on spermatogenesis
- The cause of negative feedback on the anterior puitary gland to diminish or increasing FSH
depending on the spermatogenesis is believed to be secretion by the Sertoli cells of
another hormone called inhibin -> strong effect on anterior puitary glans to inhibit the
secretion of FSH
- Inhibin is glycoprotein like LH and FSH isolated from cultured Sertoli cells-> its potent
inhibitory feedback effect on the anterior puitary glans provides an important negative
feedback mechanism for control of spermatogenesis, operating simultaneously with and in
parallel to the negative feedback mechanism for control of testosterone secretion
Female hormonal system
 - The female hormonal system, like that the one of the males consists of three hierarchies of
hormones
o Hypothalamic releasing hormone-> gonadotropin-releasing hormone (GnRH)
o The anterior puitary sex hormones -> follicle stimulating hormone (FSH) and
luteinizing hormone (LH) both of which are secreted in response to the release of
GnRH from hypothalamus
o Ovarian hormones -> estrogen and progesterone which are secreted by the ovaries
in response to two female sex hormones from anterior puitary gland
- They are secreted at different rates during different parts of the female monthly sexual
cycle
- The amount of GnRH released from hypothalamus increases and decreases much less
drastically during the monthly sexual cycle-> it’s secreted in short pulses averaging once
every 90 minutes as occurs in males
Hypothalamus secretes GnHR which causes the anterior puitary gland to secrete LH and FSH
- Intermittent, pulsatile secretion of GnHR by the hypothalamus stimulates pulsatile release
of lh from anterior puitary gland
- The hypothalamus does not secrete GnRH continuously but instead secretes it in pulses
lasting to 5-25 mins that occur very 1 to 2 h
- The neural activity that causes pulsatile release of GnRH occurs primarily in the medibasal
hypothalamus especially in nucleus arcautus -> It’s believed that these arcuate nuclei
control most female sexual activity although neurons located in the preoptic area of the
anterior hypothalamus secretes GnHR n moderate amounts
- Multiple neuronal centers in the higher brain’s limbic system transmit signals into the
arcuate nuclei to modify the intensity of GnRH release and the frequency of the pulses thus
providing a partial explanation of why psychic factors often modify female sexual function
Negative feedback effect of estrogen and progesterone to decrease LH and FSH
- Estrogen in small amounts has strong inhibitory effect on the production of both LH and
FSH
- Also when progesterone is available, the inhibitory effect of estrogen is multiplied even
though progesterone by itself has little effect
- These feedback effects seem to operate mainly on the anterior puitary gland directly but
they also operate to a lesser extent on the hypothalamus to decrease secretion of GnRH
especially by altering the frequency of the GnRH pulses
Inhibin from corpus luteum inhibits FSH and LH secretion
- In addition to feedback effects of estrogen and progesterone, other hormones seem to be
involved especially inhibin, which is secreted along with the steroid sex hormones by the
granulosa cells of the ovarian corpus luteum in the same way that Sertoli cells secrete
inhibin in male tests
- This hormone has the same effects in females as in males -> inhibiting the secretion of FSH
and to a lesser extent LH by anterior puitary glands
- It’s believed than inhibin might be important for causing the decrease in secretion of FSH
and LH at the end of the monthly female sexual cycle
Positive feedback effect on estrogen before ovulation -> preovulatory luteinizing hormone surge
- The anterior puitary gland secretes increased amounts of LH for 1-2 days 24-48 hours
before ovulation
- Experiments have shown that infusion of estrogen into a female above a critical rate for 2-
3 days during the latest part of the first half of ovarian cycle will cause rapidly accelerating
growth of the ovarian follicles as well as rapidly accelerating secretion of ovarian estrogen
 - During this period secretion of FSH and LH by anterior puitary glans are at first suppressed
- Secretion of LH then increases abruptly six fold to eightfold and secretion of FSH increases
about twofold
- The greatly increased secretion of LH causes ovulation to occur
- The cause of this abrupt surge in LH secretion is not known however some explanations are
possible
o It has been suggested that at this point in the cycle the estrogen has a peculiar
positive feedback effect of stimulating puitary secretion of LH and to a lesser extent
FSH which is in sharps contrast to the normal negative feedback effect of estrogen
that occurs during the remainder of the female monthly cycle
o The granulosa cells of the follicles begin to secrete small but increasing quantities of
progesterone a day before the preovulatory LH surge and it has been suggested
that this secretion might be a factor that stimulates the excess LH secretion
- Without this normal preovulatory surge of LH ovulation does not occur
Feedback oscillation of hypothalamic-puitary-ovarian system
1. Postovulatory secretion of the ovarian hormone and depression of the puitary
gonadotropins
o Between ovulation and beginning of menstruation the corpus luteum secrete large
quantities of progesterone and estrogen as well as inhibin
o All these hormones together have a combined negative feedback effect on the
anterior puitary gland hypothalamus causing suppression o both FSH and LH
secretion and decreasing them to their lower levels about 3-4 days before onset of
menstruation
2. Follicular growth phase
o 2-3 days before menstruation the corpus luteum has regressed to almost total
involution and secretion of estrogen, progesterone and inhibin from the corpus
luteum decreases to a low ebb which releases the hypothalamus and anterior
puitary from the negative feedback effect of these hormones
o A day or so later at about time of menstruation begins, puitary secretion of FSH
begins to increase again as much as twofold -> several days after menstruation
begins LH secretion increases slightly as well
o These hormones initiate new ovarian follicle growth and a progressive increase in
the secretion of estrogen, reaching a peak estrogen secretion at about 12.5-13 days
after the onset of new ovarian cycle
o During the 1st 11-12 days of this follicle growth, the rates of puitary secretion of
gonadotropins FSH and LH decrease slightly because of the negative feedback effect
(mainly estrogen) on anterior puitary glans
o Then there is a sudden marked increase in secretion of LH and to a lesser extent
FSH -> the increased secretion is the preovulatory surge of LH and FSH which is
followed by ovulation
3. Preovulatory surge of LH and FSH causes ovulation
o About 11.5-12 days after the onset of the monthly cycle the decline in secretion of
FSH and LH comes to an abrupt halt
o The high level of estrogens at this time (or beginning of progesterone secretion by
the follicles) s believed to cause a positive feedback stimulatory effect on the
anterior puitary which leads to a large surge in the secretion of LH and to a lesser
extent FSH
 o Whatever the cause of this preovulatory LH and FSH surge the great excessive of LH
leas to both ovulation and subsequent development of and secretion by the corpus
luteum
o The hormonal system begins its new round of secretion until the new instance of
ovulation
Ovarian cycle
- The normal reproductive years of the female are characterized by monthly rhythmical
changes in the rates of secretion of female hormones and corresponding physical changes
in the ovaries and other sexual organs
- The rhythmical pattern is called female monthly sexual/menstrual cycle that last 28 days
- It may be as short as 20 or as long as 45 days is some women although abnormal cycle
length is frequently associated with decreased fertility
- Two significant results
o Only a single ovum is normally released from the ovaries each month so normally
only a single fetus will begin to grow at a time
o Endometrium is prepared in advanced for implantation of the fertilized ovum at the
required time of the month
- The ovarian changes that occur during sexual cycle depend on FSH and LH secreted by
anterior puitary gland-> in absence of these hormones the ovaries remain inactive which is
the case during childhood where almost no puitary gonadotropic hormones are secreted
- At the age 9-12y the puitary begins to secrete progressively more FSH and LH which leads
to the onset of normal monthly sexual cycles beginning btw age of 11-15y (puberty) -> 1 st
menstrual cycle menarche
- During each month of female sexual cycle there is an increase and decrease of FSH and LH -
> these cyclical variations cause cyclical ovarian changes
- Both fsh and lh stimulate ovarian target cells by combining within highly specific fsh and lh
receptors in the ovarian target cell membranes -> activated receptors increase the cell’s
rates of secretion and usually the growth and proliferation of the cells as well
- Almost all these stimulatory effects result from activation of the cAMP second messenger
system in the cell cytoplasm which form protein kinase and multiple phosphitylation of key
enzymes that stimulate sex hormones synthesis
Follicular phase
- When a female child is
born each ovum is
surrounded by a single
layer of granulosa cells ->
ovum+ granulosa cell
sheaths = primordial
follicle
- Throughout childhood
granulosa cells are
believed to provide
nourishment for the ovum
and to secrete an oocyte
maturation inhibiting
 factor that keeps the ovum suspended in its primordial state in the prophase stage of
meiotic division
- Then after puberty when fsh and lh from anterior puitary glans begin to be secreted in
quantities the ovaries together with some of the follicles within them begin to grow
- The first stage of follicular growth is moderate enlargements of the ovum which increases
in diameter twofold/threefold -> this stage is followed by growth of twofold additional
layers of granulosa cells in some of the follicles => primary follicles
Development of antral and vesicular follicles
- During the first days of each monthly female sexual cycle the concentrations of fsh and lh
increase -> more fsh than lh
- These hormones especially fsh cause accelerated growth of 6 to 12 primary follicles each
month
- The initial effect is rapid proliferation if granulosa cells , giving rise to many more layers of
these cells
- In addition spindle cells derived from the ovary interstitium collect in serval layers outside
the granulosa cells giving rise to a second mass of cells called the theca=> divided in two
layers
o Theca interna -> the cells take on epithelioid characteristics similar to those of the
granulosa cells and develop the ability to secrete additional steroid sex hormones
(estrogen, progesterone)
o Theca externa-> develops highly vascular connective tissue capsule that becomes
the capsule of the developing follicle
- After early proliferative phase of growth the mass of granulosa cells secretes follicular
fluids that contains a high concentration of estrogen -> accumulation of this fluids causes
an antrum to appear within the mass of granulosa cells
- The early growth of the primary follicle up to antral stage is stimulated mainly by FSH alone
- Accelerated growth then occur leading to still larger follicles called vesicular follicles ->
three mechanism
o Estrogen is secreted into the follicle and causes the granulosa cells to form
increasing numbers of FSH receptors which cause a positive feedback effect
because it makes the granulosa cells even more sensitive to FSH
o The puitary fsh and the estrogen combine to promote lh receptors on the original
granulosa cells thus allowing lh stimulation to occur in addition to fsh stimulation
and creating an even more rapid increase in follicular secretion
o The increasing estrogen from the follicle plus + increasing lh from anterior puitary
gland act together to cause proliferation of the follicular thecal cells and increase
their secretion too
- Once antral follicles begin to grow very fast -> the ovum also enlarges in diameter increase
up to 10-fold, or a mass increase 1000-fold -> as the follicle enlarges the ovum remains
embedder in a mass of granulosa cells located at one pole of the follicle
Only one follicle mature fully each months, and the remainder undergo atresia
- After a week or more of growth (before ovulation) one of the follicles begins to outgrow all
the others and the remaining 5 to 11 developing follicles involute -> process called atresia
=> follicles are said to become atretic
- The cause of the atresia in unclear=> the large amounts of estrogen from the most rapidly
growing follicle act on the hypothallus to depress further enhancement of FSH secretion by
the anterior puitary gland – blocking further growth of the less well developed follicles
 - Therefore the largest follicle continue to grow because of intrinsic positive feedback effects
while other stop growing and involute
- Process of atresia is important because it normally allows only one of the follicles to grow
each month to ovulate -> prevents more than one child from developing each pregnancy
- The single follicle reaches the diameter of 1-1.5cm at the time of the ovulation and is called
mature follicle
Ovulation
- Ovulation has normally 28 days per sexual cycle occurs 14 days after the onset of
menstruation
- Shortly before ovulation, the protruding outer wall of the follicle swells rapidly and a small
area in the center of the follicular capsule called the stigma protrudes like a nipple
- In another 30 min fluid begins to ooze from the follicle through the stigma and about 2 min
later the stigma ruptures widely allowing a more viscous fluid which has occupied the
central portion of follicle to evaginate outward
- This viscous fluid carries with the ovum surrounded by a mass of several thousand small
granulosa cells called corona radiata
- A surge of LH is necessary for ovulation -> It’s necessary for final follicular growth and
ovulation
- Without this hormone even larger quantities of FSH are available the follicle will not
progress to ovulation
- 2 days before ovulation the rate of secretion of lh increases markedly, rising 6/10 fold and
peaking about 16 hours before ovulation
- Fsh also increases about twofold to threefold at the same time and the fsh and lh act
synergically to cause rapid swelling of the follicle during
the last few days before ovulation
- Lh also has specific effect on the granulosa and theca
cells -> converts them mainly to progesterone-secreting
cells => rate of secretion of estrogen begins to fall about
1 day before ovulation while increasing amount of
progesterone begin to be secreted
o Rapid growth of the follicle
o Diminishing estrogen secretion after a prolonged
phase of excessive estrogen secretion
o Initiation of progesterone that ovulation occurs
- Without the initial preovulatory surge of LH, ovulation
will not take place
- Initiation of ovulation -> large quantities of LH causes
rapid secretion of follicular steroid hormones that
contain progesterone
- Within a few hours two events occur, both of which are
necessary for ovulation
o Theca externa begins to release proteolytic
enzymes from lysosomes which cause dissolution
of the follicular capsular wall and consequent
weakening of the wall resulting in further swelling
of the entire follicle and degeneration of the
stigma
 o In the same time there is a rapid growth of the new blood vessels into the follicle
wall and at the same time prostaglandin (hormones causing dilatation) are secreted
into follicular tissue
 This two effect cause plasma transudation into the follicle which contributes to follicle
swelling
 Combination of follicle swelling and simultaneous degeneration of the stigma causes
follicle rupture with discharge of the ovum
Lutheal phase
- During first hours after expulsion of the ovum from the follicle the remaining granulosa and
theca interna cells change rapidly into lutein cells -> they enlarge in diameter two or more
times and become filled with lipid inclusions that give them a yellowish appearance
- The process is called luteiniziation and the total mass of cells together is called corpus
luteum with all developed vascular supply
- The granulosa cells in the corpus luteum develop extensive intracellular smooth
endoplasmic reticulum that form large amounts of progesterone and estrogen (more
progesterone during luteal phase)
- The theca cells form mainly the androgens androstenedione and testosterone rather than
female sex hormones
- Most of the hormone are also converted by the enzyme aromatase in the granulosa cells
into estrogen (female h)
- Corpus luteum normally grows 1.5cm in diameter reaching the stage of development 7 to 8
days after ovulation
- Then the corpus luteum begins to involute and eventually loses its secretory function and
its yellowish lipid characteristics after ovulation becoming corpus albicans -> in few weeks
the corpus albicans is replaced by connective tissue and over months reabsorbed
Luteinizing function of LH
- The change of granulosa and theca interna into lutein cells is dependent manly on LH
- The functions gives the hormone its name => luteinizing= yellowing
- Luteinization depends also o extrusion of the ovum from the follicle
- A yet uncharacterized local hormone in the follicular fluid called luteinization-inhibiting
factor, seems to hold the luteniizaton process in check until after ovulation
Secretion of corpus luteum
- Corpus luteum is a highly secretory organ secreting large amounts of estrogen and
progesterone
- Once lh has acted on the granulosa and theca cells to cause luteinization the newly formed
lutein cells seem to be programmed to go through a preordained sequence of proliferation,
enlargement, secretion and degeneration => 12 days
Onset next ovarian cycle
- Estrogen in particular and progesterone less secreted by corpus luteum during the luteal
phase have strong feedback effects on the anterior puitary gland to maintain low secretory
rates of both FSH and LH
- The lutein cells secrete small amounts of the hormone inhibin (the same secreted by
Sertoli cells of testes) -> this inhibits fsh secretion by anterior puitary glans
- Low blood concentration of both fsh and lh result, and loss of these hormones finally
causes the corpus luteum to degenerate completely => involution of the corpus luteum
- Final involution occurs at the end of almost 12 days of corpus luteum life which is around
the 25th day of the normal sexual cycle 2 days before menstruation begins
 - Now sudden cessation of secretion of estrogen and progesterone and inhibin by the corpus
luteum removes the feedback inhibition of the anterior puitary glans allowing it to secrete
increasing amounts of fsh and lh again -> lh and fsh initiate the growth of new follicles
beginning a new ovarian cycle
Endometrial cycle
- Associated with monthly cyclical production of estrogens and progesterone by the ovaries
is an endometrial cycle in the lining of uterus that operates through
o Proliferation of uterine endometrium
o Development of secretory change in endometrium
o Desquamation of endometrium = menstruation
Proliferative phase
- Proliferative or estrogen phase of endometrial cycle occurs before ovulation
- At the beginning of each monthly cycle most of the endometrium has been desquamates
by menstruation
- After menstruation only a thin layer of endometrial stroma remains and the only epithelial
cells that are left are those located in the remaining deeper portions of the glands and
crypts of endometrium
- Under the influence of estrogens secreted in increasing quantities by ovaries during the
first part of ovarian cycle the stromal cells and the epithelial cells proliferate rapidly-> the
endometrial surface is re-epithelialized within 4 to 7 days after the beginning of
menstruation
- During the next week and half, before ovulation occurs, the endometrium increases in
thickness due to increasing of numbers of stromal cells and to progressive growth of the
endometrial glands and new blood vessels into endometrium
- At the time of ovulation the endometrium is 3-5mm thick
- The endometrial glands especially those of the cervical region secretes thin, stringy mucous
-> the mucous strings align themselves along the length of the cervical canal forming
channels that help guide sperm in the proper direction from vagina to uterus
Secretory phase
- Secretory or presentational phase of the endometrial cycle occurs after ovulation
- During the most latter half of the monthly cycle, after ovulation occurs, progesterone and
estrogen together are secreted in large quantities by corpus luteum
- The estrogen causes additional cellular proliferation in the endometrium during this phase
- Progesterone causes marked swelling and secretory development of the endometrium
- The glands increases in tortuosity and an excess of secretory substances accumulates in the
glandular epithelial cells
- The cytoplasm of stromal cells increases, lipid and glycogen deposit increase in the stromal
cells and the blood supply to the endometrium increases in proportion to the developing
secretory activities
- At the peak of secretory phase about 1 week after ovulation the endometrium has
thickness of 5-6mm
- The purpose of all these endometrial changes is to produce a highly secretory
endometrium that contains large amounts of stored secretory endometrium that contains
large amounts of stored nutrients to provide appropriate conditions for implantation of a
fertilized ovum during the latter half of monthly cycle
- From the time a fertilized ovum enters the uterine cavity from fallopian tube (3-4 days
after ovulation) until the ovum implants (7-9 after ov) the uterine secretions, called uterine
milk, provide nutrition for the early dividing ovum
 - Once the ovum implants in the endometrium, the trophoblastic cells on the surface of the
implanting ovum (in blastocyst stage) begin to digest the endometrium and absorb the
endometrial stores substance thus making great quantities of nutrients available to the
early implanting embryo
Menstruation
- If the ovum is not fertilized, about 2 days before the end of the monthly cycle, the corpus
luteum in the ovary involutes and the ovarian hormones decrease to low levels of secretion
-> menstruation follows
- It’s caused by the reduction of estrogen and progesterone (especially progesterone) at the
end of the monthly ovarian cycle
- The first effect is decreased stimulation of the endometrial cells by these two hormones,
followed rapidly by involution of the endometrium to about 65% of its previous thickness
- During 24 hours preceding the onset of menstruation the tortuous blood vessels leading to
the mucosal layers of endometrium become vasospastic, maybe because of some effect of
involution, such as release of a vasoconstrictor material (possibly one of the
vasoconstrictor types of prostaglandins that are present in abundance at this time)
- The vasospasm, the decrease in nutrients to the endometrium and the loss of hormonal
stimulation initiate necrosis in the endometrium especially of the blood vessels-> blood at
first seeps into vascular layer of endometrium and the hemorrhagic areas grow rapidly
over a period of 24-36 hours
- The necrotic outer layers of endometrium separate from the uterus at sites of the
hemorrhages until about 48 h after onset of menstruation all the superficial layers of
endometrium have desquamated
- The mass of desquamated tissue and blood in the uterine cavity + contractile effects of
prostaglandins or other substance in decaying desquamate, all acting together initiate
uterine contractions that expel the uterine contents
- During normal menstruation approximately 40ml of blood and 35ml of serous fluid are lost
- The menstrual fluid is normally non clotting because a fibrinolysis is released along with the
necrotic endometrial material
- If excessive bleeding occurs from uterine surface the quantity of fibrinolysis may not be
sufficient to prevent clotting -> presence of clots during menstruation is a clinical evidence
of uterine disease
- Within 4/7 days after menstruation starts the loss of blood ceases because by this time the
endometrium has become re-epithelized
- During menstruation large numbers of leukocytes are released along with necrotic material
and blood -> uterus is highly resistant to infection during menstruation even though
endometrial surfaces are denuded
Estrogen
- In non-pregnant female estrogens are secreted in significant quantities only by the ovaries
although a minute amounts are also secreted by adrenal cortices
- During pregnancy large quantities of estrogen are also secreted by placenta
- Only three estrogen are present in significant quantities in the plasma of female
o -estradiol -> principal estrogen secreted by the ovaries
o Estrone -> small amounts are also secreted but most of this s formed in peripheral
tissue from androgens secreted by adrenal cortices and by ovarian thecal cells
o Estriol -> weak estrogen, oxidative product derived from both estradiol and estrone
with conversion occurring mainly in liver
 - The estrogenic potency of -estradiol is 12 times that of estrone and 80 times that of
estriols
Functions
- Primary function of estrogen is to cause cellular proliferation and growth of the tissues of
sex organs and other tissues related to reproduction
- Uterus and external female organs-> during childhood estrogen is secreted only in minor
quantities but at puberty the quantity secreted under the influence of the puitary
gonadotropic hormones increases 20-fold of more
o Female sex organs change from those of a child to those of adult
o Ovaries, fallopian tubes, uterus and vagina all increase several time in size
o Also external genitalia enlarge with deposition of fat in the mons pubis and labia
majora and enlargement of labia minora
o Estrogens changes the vagina epithelium from cuboidal into stratified which is more
resistant to trauma and infection (children vaginal infections can be cured by
administrating estrogen resulting in increased resistance of vaginal epithelium)
o In the firsts year after puberty the size of uterus increases in size
o It causes changes in uterine endometrium-> proliferation of endometrial stroma
and greatly increased development of endometrial glans which will later provide
nutrition to the implanted ovum
- Fallopian tubes -> estrogen effect on the mucosal lining of the fallopian tubes is similar to
its effect on endometrium
o They cause the glandular tissue of this lining to proliferate and they cause number
of ciliated epithelial cells that line the fallopian tube to increase
o Also activity of the cilia is considerably enhances
o The cilia always beat toward the uterus which help propel the fertilized ovum in
that direction
- Breasts-> primordial breasts of female and males are the same and under the influence of
the appropriate hormones also the masculine breast during the first 20 decades of life can
develop to produce milk in the same manner as female
o Estrogen causes development of stromal tissues of breasts, grow of an extensive
ductile system, deposition of fat in breasts
o The lobules and alveoli of breast develop to a light extend under the influence of
estrogen alone but it’s progesterone and prolactin that cause the ultimate
determinative growth and function of these structures
 Estrogen initiate the growth of breast and milk-producing apparatus and they are also
responsible for the characteristics growth and external appearance of mature female
breasts
 They do not complete the job of converting the breasts into milk-producing organs
- Skeleton-> estrogen inhibits osteoclast activity in the bones and therefore stimulate bone
growth
o Part of this effect is due to stimulation of osteoprotegerin which is also called
osteoclastogenesis inhibitory factor which is a cytokine that inhibits bone
resorption
o At puberty when female enters her reproductive years her growth in height
becomes rapid for several years
o Estrogens have another effect on skeletal growth -> they cause uniting of epiphyses
with shafts of long bones-> effect much more stronger than the similar effect of
testerone in males
 o Growth of female usually ceases several years earlier than growth of female
- Osteoporosis in old age-> after menopause almost no estrogen are secreted by ovaries
o This deficiency leads to increased osteoclast activity in the bones, decreased bone
matrix and decreased deposition of bone calcium and phosphate
o In some women this effect is extremely severe and the resulting condition is
osteoporosis -> because it can greatly weaken the bones and lead to bone fracture
especially of vertebrae many postmenopausal women are treated prophylactically
with estrogen replacement to prevent osteoporotic effects
- Increasing protein deposition-> estrogen causes slight increase in total body protein which
is evidenced by a positive nitrogen balance when estrogen are administered
o This effect mainly results from growth-promoting effect of estrogen on the sexual
organs, bones, and few other tissues of the body
o The enhances protein deposition caused by testosterone is much more general and
much more powerful than that caused by estrogen
- Increasing body metabolism and fat deposition -> estrogen increases the whole body
metabolic rate but only 1/3 as much as the increased caused by male sex hormone
testosterone
o Estrogen causes deposition of increased quantities of fat in the subcutaneous
tissues -> percentage of the body fat in female is greater than in males body which
contains more proteins
o In addition of fat in breast and subcutaneous tissue estrogen causes fat deposition
in the buttocks and thighs
- Hair distribution-> it doesn’t greatly affect hair distribution but hair develops in pubic
region and in axillae after puberty
o Androgens formed in increased quantities by the female adrenal glands after
puberty are mainly responsible for development of hair
- Skin-> estrogen causes the skin to develop a texture that is soft and usually smooth but
even so the skin of a woman is thicker than the one of a child or castrated female
o It causes the skin to become more vascular which is often associated with increased
warmth of the skin and also promote greater bleeding of cut surfaces than is
observed in men
- Electrolyte balance-> estrogen like aldosterone and some other adrenocortical hormones
causes sodium and water retention by kidney tubules
o This effect is slight and rarely of significance but during pregnancy the tremendous
formation of estrogen by placenta may contribute to body fluid retention
Progesterone
- Progesterone is the most important of the progestins
- Small amount of progestin 17--hydroxyprogesterone, are secreted along with
progesterone and have essentially the same effects
- In non-pregnant female progesterone is usually secreted in significant amounts only during
latter half of each ovarian cycle, when is secreted by the corpus luteum
- Large amount of progesterone are also secreted by the placenta during pregnancy
especially after the 4th month of gestation
Functions
- Promoting secretory changes in the uterus-> major function is to promote secretory
changes in the uterine endometrium during the latter half of the monthly female sexual
cycle -> prepares the uterus for implantation of the fertilized ovum
o This effect is in connection with the endometrial cycle of uterus
 o Progesterone also decreases frequency and intensity of uterine contractions
helping to prevent expulsion of the implanted ovum
- Fallopian tubes-> promotes increased secretion by the mucosal lining of the fallopian
tubes
o This secretion are necessary for nutrition of the fertilized, dividing ovum ad it
transverses the fallopian tube before implantation
- Breasts-> promotes developments of the lobules and alveoli of the breasts causing alveolar
cells to proliferate, enlarge and become secretory
o Progesterone do not cause the alveoli to secrete milk which is secreted only after
the prepared breasts is further stimulated by prolactin from anterior puitary gland
o It causes also the breast to swell -> part of the swelling is due to secretory
development in the lobules and alveoli but part also results from increased fluid in
tissue
Hormones during gestation
- In pregnancy the placenta forms large quantities of human chorionic gonadotropin,
estrogen, progesterone and human chorionic somatomammotropin which are all essential
to a normal pregnancy
- Human chorionic gonadotropin causes persistence of the corpus luteum and prevents
menstruation
- Menstruation normally occurs in non-pregnant woman about 14 days after ovulation at
which time most of the endometrium of the uterus sloughs away from the uterine wall and
is expelled to the exterior
- If this should happen after an ovum has implanted, the pregnancy would terminate -> this
sloughing is prevented by the secretion of human chorionic gonadotropin by the newly
developing embryonic tissues
- Coincidental with the development of the trophoblast cells from the early fertilized ovum,
the hormones human chorionic gonadotropin is secreted by the syncytial trophoblast cells
into the fluids of the mother
- The secretion of this hormone can be measured in the blood 8-9 days after ovulation
shortly after the blastocyst implants in the endometrium-> the rate of secretion rises
rapidly to reach maximum at 10-12 weeks of pregnancy, decreases back to a lower value
by 16-20 weeks and continues at this level for the remainder of the pregnancy
Function of human chorionic gonadotropin
- Human chorionic gonatropin is a glycoprotein having a molecular weight of 39000 and
much the same molecular structure and function as LH secreted by anterior puitary
- The most important function is to prevent involution of corpus luteum at the end of the
monthly female cycle-> It causes the corpus luteum to secrete even larger quantities of
progesterone and estrogen for the next few months
- These sex hormones prevent menstruation and causes the endometrium to continue to
grow and store large amounts of nutrients rather than being shed in the menstruum
- The decidual like cells that develop in the endometrium during the normal female sexual
cycle become actual decidual cells at about time that the blastocyst implants
- Under the influence of chorionic gonadotropin the corpus luteum in the mother’s ovary
grows to about twice the initial size by a months after pregnancy begins
- Its continued secretion of estrogen and progesterone maintains the decidual nature of the
uterine endometrium which is necessary for the early development of fetus
- If the corpus luteum is removed approximately before 7th weeks of pregnancy spontaneous
abortion almost always occurs sometimes even up to the 12th week
 - After that time the placenta secretes sufficient amounts of estrogen and progesterone to
maintain pregnancy for the remainder gestation period
- The corpus luteum involutes slowly after the 13th-17th week
- Human chorionic gonadotropin stimulates the male fetal testis to produce testosterone
o It also exerts an interstitial cell-> stimulating effect on the testes of male fetus
resulting in the production of testosterone of the male fetus until the time of birth
o This small secretion of testosterone during gestation is what causes the fetus to
grow male sex organs instead of female organs
o Near the end of pregnancy the testosterone secreted by the testis also causes the
testis to descend into scrotum
Secretion of estrogens by placenta
- The placenta like corpus luteum secretes both estrogen and progesterone -> they’re
secreted by the syncytial trophoblast cells of the placenta
- Towards the end of pregnancy the daily production of placenta estrogens increases to
about 30 times the mother’s normal level of production
- However the secretion of estrogens by the placenta is different from the secretion by
ovaries -> estrogen by placenta are not synthesized de novo from basic substrates of
placenta instead they are formed almost entirely from androgenic steroid compounds
dehydroepiandrosterone and 16-hydroxydehydroepiandrosterone which are formed both
in the mother’s adrenal glands and in the adrenal glands of the fetus
- These weak androgens are transported by the blood to placenta and converted by the
trophoblast cells into estradiol, estrone and estriol
Function of estrogen in pregnancy
- During pregnancy extreme quantities of estrogen causes
o Enlargement of the mother’s uterus
o Enlargement of mother’s breasts and growth of the breasts ductal structure
o Enlargement of mother’s female external genitalia
- The estrogens also relax the pelvic ligaments of the mother so that the sacroiliac joints
become relatively limber and symphysis pubic more elastic -> these changes allow easier
passage of the fetus through birth canal
- There is much reason to believe that estrogen also effect many general aspects of fetal
development during pregnancy e.g. affecting rate of cell reproduction in early embryo
Secretion of progesterone by placenta
- It’s essential for successful pregnancy, just as important as estrogen -> in addition to be
secreted at the beginning of pregnancy by corpus luteum it’s secreted later in big
quantities by placenta
- The following effects of progesterone are essential for normal progression of pregnancy
o Causes decidual cells to develop in uterine endometrium-> important role in
nutrition of early embryo
o Decreases contractility of the pregnant uterus -> preventing uterine contraction
from causing spontaneous abortion
o Contributes to development of the conceptus even before implantation because it
specifically increases secretion of the mother’s fallopian tubes and uterus to
provide appropriate nutritive matter for developing morula (16-32 blastomeres
formed before blastula) and blastocyst
o There is also reason to believe that progesterone affects the cell cleavage in early
developing embryo
 o Progesterone secreted during pregnancy helps progesterone prepare the mother’s
breast for lactation
Human chorionic somatomammotropin
- Human chorionic somatomammotropin begins to be secreted by the placenta at about 5 th
week of pregnancy
- Secretion of this hormone increases progressively throughout the remainder of pregnancy
in direct proportion to the weight of the placenta
- Although the function are uncertain it’s secreted in quantities several times greater than
that of all other pregnancy hormones combines
- Several possible important effects
o When administered to animals it causes at least partial development of the breasts
and in some instances causes lactation -> it’s also named human placental lactogen
and it was believed to have functions similar to those of prolactin but attempts to
use it to promote lactation in humans have not been successful
o It has weak actions similar to those of growth hormone causing formation of
protein tissues in the same way that growth hormone does
It has a chemical structure similar to that of growth hormone but 100 times as
much as human chorionic somatomammotropin as growth hormone is required to
promote growth
o Causes decreased insulin sensitivity and decreased utilization of glucose in the
mother -> makes large quantities of glucose available to the fetus
Because glucose is the major substrate used by the fetus to energize its growth the
possible importance of such hormonal effect is obvious
o The hormone promotes the release of free fatty acids from the fat stores of the
mother -> provides an alternative source of energy for the mother’s metabolism
during pregnancy
 It appears that human chorionic somatomammotropin is a general metabolic hormone
that has specific nutritional implication for both mother and fetus
Oxytocin during parturition
- Oxytocin causes contraction of the uterus
- It’s a hormone secreted by neurohypophysis specifically causes uterine contraction
- There are four reason to believe that oxytocin might be important in increasing
contractility for uterus near term
o Uterine muscle increases its oxytocin receptor and therefore increases its
responsiveness to a given dose of oxytocin during the latest few month of
pregnancy
o The rate of oxytocin secretion by the neurohypophysis is considerably increased at
the time of labor
o Although hypophysectomized animals can still deliver their young at term labor is
prolonged
o Experiments in animals indicate that irritation or stretching of uterine cervix as
occurs during labor, can cause neurogenic reflex through the paraventricular and
supraoptic nuclei of the hypothalamus that cause the posterior puitary/
neurohypophysis to increase secretion of oxytocin
- Positive feedback theory suggest that stretching of the cervix by the fetus’ head finally
becomes great enough to elicit a strong reflex increase in contractility of the uterine body -
> this process repeats until the baby is expelled
 - First, labor contraction obey all the principles of positive feedback -> once the strength of
uterine contraction becomes greater than a critical value each contraction leads to a
subsequent contraction that become stronger and stronger until maximum effect is
achieved
- Second, two known types of positive feedback increase uterine contractions during labor
o Stretching of the cervix causes the entire body of the uterus to contracts and this
contraction stretches the cervix even more because of the downward thrust of the
baby’s head
o Cervical stretching also causes the puitary gland to secrete oxytocin
- We can assume that multiple factors increase the contractility of the uterus toward the
end of pregnancy -> eventually a uterine contraction becomes strong enough to irritate the
uterus especially the cervix and this irritation increases uterine contractility still more
because positive feedback
Regulation of lactation
- Although estrogen and progesterone are essential for the physical development of breast
during pregnancy a specific effect of both these hormones is to inhibit the actual secretion
of milk
- The hormone prolactin has exactly the opposite effect and promotes milk secretion
- Prolactin is secreted by the mother’s anterior puitary gland and its concentration in her
blood rises steadily from the 5th week of pregnancy until birth of baby at which time it has
risen to 10-20 times the normal non pregnant level
- The placenta secretes large quantities of human chorionic somatomammotropin which
probably has lactogenic properties -> supports the prolactin from the mother’s puitary
during pregnancy
- Because of the suppressive effects of estrogen and progesterone no more than few mm of
fluid are secreted each day until the baby is born -> the fluid secreted during last few days
before and after parturition is called colostrum and contains essentially the same
concentration of proteins and lactose as milk but it has almost no fat and its maximum rate
of production is about 1/100 the subsequent rate of milk production
- Immediately after the baby is born the sudden loss of both estrogen and progesterone
secretion from placenta allows the lactogenic effect of prolactin from the mother’s puitary
gland to assume its natural milk promoting role -> in next 1-7 days the breasts begin to
secrete copious quantities of milk instead of colostrum
- This secretion of milk requires an adequate background secretion of most of the mother0s
other hormones as well -> growth hormones, cortisol, parathyroid hormone and insulin =>
necessary to provide the amino acids, fatty acids, glucose and calcium required for
formation of milk
- After birth , the basal level of prolactin secretion returns to the non-pregnant level the next
few weeks -> each time the mother nurses the baby a nervous signal from the nipples to
hypothalamus causes a 10- to 20-fold surge of prolactin secretion that last for about 1 hour
- This prolactin acts on the mother’s breast to keep the mammary glands secreting milk into
the alveoli for the subsequent nursing periods
Ejection process in milk secretion
- Milk is secreted continuously into alveoli of the breasts but it does not flow easily from the
alveoli into the ductal system and therefore does not continually leak from the nipples
- The milk must be ejected from the alveoli into the ducts before the baby can obtain it-> the
ejection is caused by combined neurogenic and hormonal reflex that involves the posterior
puitary hormone oxytocin
- When the baby sucks it receives virtually no milk for the first half minute -> sensory
impulses must be first transmitted through somatic nerves from the nipples to the
mother’s spinal cord and then to her hypothalamus where they cause nerve signals that
promote oxytocin secretion at the same time that they cause prolactin secretion
- The oxytocin is carried in the blood to the breast where it causes myoepithelial cells that
surrounds the alveoli to contract-> expressing the milk from the alveoli into the ducts at a
pressure of +10 to 20 mm Hg
- Within 30 s to 1 min after the baby starts to suckle, milk begins to flow => process called
milk ejection or milk let-down
- Suckling on one breast causes milk flow not only in that breast but also in the opposite
breast
- It’s interesting that fondling of the baby by the mother or hearing the baby crying often
givers enough of an emotional signal to the hypothalamus to cause milk ejection