Endocrine System

Endocrine System: Overview

• Endocrine system – the body’s second great controlling system which influences metabolic

activities of cells by means of hormones

• Endocrine glands – pituitary, thyroid, parathyroid, adrenal, pineal, and thymus glands

• The pancreas and gonads produce both hormones and exocrine products

• The hypothalamus has both neural functions and releases hormones

• Other tissues and organs that produce hormones – adipose cells, pockets of cells in the walls

of the small intestine, stomach, kidneys, and heart

Hormones

• Hormones – chemical substances secreted by cells into the extracellular fluids

• Regulate the metabolic function of other cells

• Have lag times ranging from seconds to hours

• Tend to have prolonged effects

• Are classified as amino acid-based hormones, or steroids

• Eicosanoids – biologically active lipids with local hormone–like activity

Types of Hormones
• Amino acid–based – most hormones belong to this class, including:

• Amines, thyroxine, peptide, and protein hormones

• Steroids – gonadal and adrenocoritcal hormones

• Eicosanoids – leukotrienes and prostaglandins

Hormone Action
• Hormones alter cell activity by one of two mechanisms

• Second messengers involving:

• Regulatory G proteins

• Amino acid–based hormones

• Direct gene activation involving steroid hormones

• The precise response depends on the type of the target cell

Mechanism of Hormone Action

• Hormones produce one or more of the following cellular changes:

• Alter plasma membrane permeability

• Stimulate protein synthesis

• Activate or deactivate enzyme systems

• Induce secretory activity

• Stimulate mitosis

Amino Acid–Based Hormone Action: cAMP Second Messenger

• Hormone (first messenger) binds to its receptor, which then binds to a G protein

• The G protein is then activated as it binds GTP, displacing GDP

• Activated G protein activates the effector enzyme adenylate cyclase

• Adenylate cyclase generates cAMP (second messenger ) from ATP

• cAMP activates protein kinases, which then cause cellular effects

Amino Acid–Based Hormone Action:

PIP-Calcium

• Hormone binds to the receptor and activates G protein

• G protein binds and activates a phospholipase enzyme

• Phospholipase splits the phospholipid PIP2 into diacylglycerol (DAG) and IP3 (both act as

second messengers)

• DAG activates protein kinases; IP3 triggers release of Ca2+ stores

• Ca2+ (third messenger) alters cellular responses

Amino Acid–Based Hormone Action:

PIP-Calcium

Steroid Hormones

• Steroid hormones and thyroid hormone diffuse easily into their target cells

• Once inside, they bind and activate a specific intracellular receptor

• The hormone-receptor complex travels to the nucleus and binds a DNA-associated receptor

protein

• This interaction prompts DNA transcription, to producing mRNA

• The mRNA is translated into proteins, which bring about a cellular effect

Steroid Hormones

Hormone–Target Cell Specificity

• Hormones circulate to all tissues but only activate cells referred to as target cells

• Target cells must have specific receptors to which the hormone binds

• These receptors may be intracellular or located on the plasma membrane

• Examples of hormone activity

• ACTH receptors are only found on certain cells of the adrenal cortex

• Thyroxin receptors are found on nearly all cells of the body

Target Cell Activation

• Target cell activation depends upon three factors
• Blood levels of the hormone

• Relative number of receptors on the target cell

• The affinity of those receptors for the hormone

• Up-regulation – target cells form more receptors in response to the hormone

• Down-regulation – target cells lose receptors in response to the hormone

Hormone Concentrations in the Blood

• Concentrations of circulating hormone reflect:

• Rate of release

• Speed of inactivation and removal from the body

• Hormones are removed from the blood by:

• Degrading enzymes

• The kidneys

• Liver enzyme systems

Control of Hormone Synthesis and Release

• Blood levels of hormones:

• Are controlled by negative feedback systems

• Vary only within a narrow desirable range

• Hormones are synthesized and released in response to:

• Humoral stimuli

• Neural stimuli

• Hormonal stimuli

Humoral Stimuli
• Humoral stimuli – secretion of hormones in direct response to changing blood levels of ions

and nutrients

• Example: concentration of calcium ions in the blood

• Declining blood Ca2+ concentration stimulates the parathyroid glands to secrete PTH

(parathyroid hormone)

• PTH causes Ca2+ concentrations to rise and the stimulus is removed

Neural Stimuli
• Neural stimuli – nerve fibers stimulate hormone release

• Preganglionic sympathetic nervous system (SNS) fibers stimulate the adrenal medulla to

secrete catecholamines

Hormonal Stimuli

• Hormonal stimuli – release of hormones in response to hormones produced by other

endocrine organs

• The hypothalamic hormones stimulate the anterior pituitary

• In turn, pituitary hormones stimulate targets to secrete still more hormones

Nervous System Modulation

• The nervous system modifies the stimulation of endocrine glands and their negative feedback

mechanisms

• The nervous system can override normal endocrine controls

• For example, control of blood glucose levels

• Normally the endocrine system maintains blood glucose

• Under stress, the body needs more glucose

• The hypothalamus and the sympathetic nervous system are activated to supply ample glucose

Location of the Major Endocrine Glands

• The major endocrine glands include:

• Pineal gland, hypothalamus, and pituitary

• Thyroid, parathyroid, and thymus

• Adrenal glands and pancreas

• Gonads – male testes and female ovaries

Major Endocrine Organs: Pituitary (Hypophysis)

• Pituitary gland – two-lobed organ that secretes nine major hormones

• Neurohypophysis – posterior lobe (neural tissue) and the infundibulum

• Receives, stores, and releases hormones from the hypothalamus

• Adenohypophysis – anterior lobe, made up of glandular tissue

• Synthesizes and secretes a number of hormones

Pituitary-Hypothalamic Relationships: Posterior Lobe

• Posterior lobe – a downgrowth of hypothalamic neural tissue

• Has a neural connection with the hypothalamus (hypothalamic-hypophyseal tract)

• Nuclei of the hypothalamus synthesize oxytocin and antidiuretic hormone (ADH)

• These hormones are transported to the posterior pituitary

Pituitary-Hypothalamic Relationships: Anterior Lobe

• The anterior lobe of the pituitary is an outpocketing of the oral mucosa

• There is no direct neural contact with the hypothalamus

• There is a vascular connection, the hypophyseal portal system, consisting of:

• The primary capillary plexus

• The hypophyseal portal veins

Adenohypophyseal Hormones

• The six hormones of the adenohypophysis:

• Are abbreviated as GH, TSH, ACTH, FSH, LH, and PRL

• Regulate the activity of other endocrine glands

• In addition, pro-opiomelanocortin (POMC):

• Has been isolated from the pituitary

• Is enzymatically split into ACTH, opiates, and MSH

Activity of the Adenohypophysis

• The hypothalamus sends chemical stimulus to the anterior pituitary

• Releasing hormones stimulate the synthesis and release of hormones

• Inhibiting hormones shut off the synthesis and release of hormones

• The tropic hormones that are released are:

• Thyroid-stimulating hormone (TSH)

• Adrenocorticotropic hormone (ACTH)

• Follicle-stimulating hormone (FSH)

• Luteinizing hormone (LH)

Growth Hormone (GH)

• Produced by somatotropic cells of the anterior lobe that:

• Stimulate most cells, but target bone and skeletal muscle

• Promote protein synthesis and encourage the use of fats for fuel

• Most effects are mediated indirectly by somatomedins

• Antagonistic hypothalamic hormones regulate GH

• Growth hormone–releasing hormone (GHRH) stimulates GH release

• Growth hormone–inhibiting hormone (GHIH) inhibits GH release

Metabolic Action of Growth Hormone

• GH stimulates liver, skeletal muscle, bone, and cartilage to produce insulin-like growth

factors

• Direct action promotes lipolysis and inhibits glucose uptake

Thyroid Stimulating Hormone (Thyrotropin)

• Tropic hormone that stimulates the normal development and secretory activity of the thyroid

gland

• Triggered by hypothalamic peptide thyrotropin-releasing hormone (TRH)

• Rising blood levels of thyroid hormones act on the pituitary and hypothalamus to block the

release of TSH

Adrenocorticotropic Hormone (Corticotropin)

• Stimulates the adrenal cortex to release corticosteroids

• Triggered by hypothalamic corticotropin-releasing hormone (CRH) in a daily rhythm

• Internal and external factors such as fever, hypoglycemia, and stressors can trigger the release

of CRH

Gonadotropins

• Gonadotropins – follicle-stimulating hormone (FSH) and luteinizing hormone (LH)

• Regulate the function of the ovaries and testes

• FSH stimulates gamete (eggs or sperm) production

• Absent from the blood in prepubertal boys and girls

• Triggered by the hypothalamic gonadotropin-releasing hormone (GnRH) during and after

puberty

Functions of Gonadotropins

• In females

• LH works with FSH to cause maturation of the ovarian follicle

• LH works alone to trigger ovulation (expulsion of the egg from the follicle)

• LH promotes synthesis and release of estrogens and progesterone

• In males

• LH stimulates interstitial cells of the testes to produce testosterone

• LH is also referred to as interstitial cell-stimulating hormone (ICSH)

Prolactin (PRL)

• In females, stimulates milk production by the breasts

• Triggered by the hypothalamic prolactin-releasing hormone (PRH)

• Inhibited by prolactin-inhibiting hormone (PIH)

• Blood levels rise toward the end of pregnancy

• Suckling stimulates PRH release and encourages continued milk production

The Posterior Pituitary and Hypothalamic Hormones

• Posterior pituitary – made of axons of hypothalamic neurons, stores antidiuretic hormone

(ADH) and oxytocin

• ADH and oxytocin are synthesized in the hypothalamus

• ADH influences water balance

• Oxytocin stimulates smooth muscle contraction in breasts and uterus

• Both use PIP second-messenger mechanisms