The Endocrine System

Basic Morphophysiology EMIS ITESM

Department of Basic Sciences

Introduction
Maintenance of homeostasis involves coordinating activities of organs and systems throughout the body Endocrine system and Nervous system are the mayor control systems

Introduction
The Endocrine System is responsible for the maintenance of growth, metabolism, development, puberty and mood. The endocrine and nervous system can work together or alone to perform the same general functions: to monitor and adjust physiologic activities

Introduction
Summary: Major control systems:
Endocrine and nervous system work together Function: to maintain homeostasis

Both use
specific communication methods affect specific target organs

Their methods and effects differ.

Introduction
In general, the nervous system performs shortterm very specific responses to environmental stimuli - chemical messengers are neurotransmitters The endocrine system regulates longer-term, ongoing metabolic processes throughout the body - chemical messengers are hormones

Comparison of Nervous and Endocrine Systems Control

Characteristic Mediator Molecules Nervous System Neurotransmitters released locally Endocrine System Hormones delivered throughout the body by the blood Usually far from site of release Cells throughout the body

Site of Mediator Action Close to site of release Types of target cells Muscle (smooth, cardiac, and skeletal) cells, gland cells, other neurons

Time to onset of action Within milliseconds

Duration of Action Typically briefer (milliseconds)

Seconds hours days

Generally longer (seconds to days)

Glands
A. Exocrine gland Ducts Lumen and surfaces B. Endocrine gland Chemical messengers Blood stream

Endocrine System

Pituitary
The hypothalamus-pituitary unit is the most dominant portion of the entire endocrine system. The output of the hypothalamus-pituitary unit regulates the function of the thyroid, adrenal and reproductive glands and also controls somatic growth, lactation, milk secretion and water metabolism. The pituitary gland lies in a pocket of bone at the base of the brain, just below the hypothalamus to which it is connected by a stalk containing nerve fibers and blood vessels. The pituitary is composed to two lobes-anterior and posterior.

Pituitary

Pituitary
Anterior pituitary derived from outpouching of pharyngeal mucosa Eventually pinches off and becomes separate from pharynx Posterior pituitary derived from outgrowth of hypothalamus

Pituitary

Posterior pituitary remains connected to hypothalamus by infundibular stalk

Pituitary
The anterior, intermediate, and posterior lobes of the pituitary gland are actually three more or less separate endocrine organs. The intermediate lobe is rudimentary in humans. It is separated from the anterior lobe by the remains of Rathke's pouch.

Gross Anatomy - Histological Organization of the Pituitary Gland

Anterior Pituitary
All are peptide hormones All are trophic hormones: Stimulate a target endocrine gland to secrete increased amounts of its own hormone (except PRL).

Anterior Pituitary
ACTH, prolactin, and growth hormone are simple polypeptides or proteins. TSH, LH, and FSH are glycoproteins made up of two subunits ( and ).

All of the subunits of these hormones are products of a single gene and have the same amino acid composition, although their carbohydrate residues vary.
The subunits, which are produced by separate genes and differ in structure, confer hormonal specificity. The subunits are remarkably interchangeable, and hybrid molecules can be created.

Pituitary Hormones

Hypothalamic Pituitary Axis

Pituitary Portal System

Hypothalamic-hypophyseal portal system links anterior pituitary to hypothalamus. In most parts of the body, arteries are connected with veins through capillary plexus. Nonetheless, in certain areas, we can find special functional adaptations to this system. When capillaries connect with vessels that, in turn, offer a second set of capillaries before connecting with systemic veins, this disposition is called a portal system.

Pituitary Portal System

Parvicellular neurosecretory cells secrete releasing factors into capillaries of the pituitary portal system at the median eminence which are then transported to the anterior pituitary gland to regulate the secretion of pituitary hormones.

Pituitary Portal System

The anterior pituitary is made up of interlacing cell cords and an extensive network of sinusoidal capillaries. The endothelium of the capillaries is fenestrated, like that in other endocrine organs. The cells contain granules of stored hormone that are extruded from the cells by exocyrosis. The granules presumably break down in the peri-capillary space, and their contents enter the capillaries.

Posterior Pituitary
Posterior pituitary is made up of endings of the axons that arise from cell bodies in the supraoptic and paraventricular nuclei and pass to the posterior pituittary via the hypothalamohypophysial trat. Most of the supraoptic fiber end in the posterior lobe itself whereas some of the paraventricular fibers end in the median eminence. There are also pituicytes, stellate cells which are modified astrocyres.

Posterior Pituitary
Hormones secreted by posterior pituitary are synthesized in nerve cell bodies in hypothalamus and secreted by axonal terminals in posterior pituitary, and from there into veins, which carry them into systemic circulation Hormones secreted by posterior pituitary are :

1. ADH (vasopressin) 2. Oxytocin

Both are peptide hormones.

Hypothalamic Control over Endocrine Organs

Hypothalamic Control over Endocrine Organs

Characteristics of hypothalamic releasing hormones 1. 2. 3. 4. 5. 6. Secretion in pulses Act on specific membrane receptors Transduce signals via second messengers Stimulate release of stored pituitary hormones Stimulate synthesis of pituitary hormones Stimulates hyperplasia and hypertophy of target cells 7. Regulates its own receptor

Pituitary
Hypothalamic releasing hormone Corticotropin releasing hormone (CRH) Thyrotropin releasing hormone (TRH) Growth hormone releasing hormone (GHRH) Somatostatin Gonadotropin releasing hormone (GnRH) a.k.a LHRH Prolactin releasing hormone (PRH) Prolactin inhibiting hormone (dopamine) Effect on pituitary

Stimulates ACTH secretion

Stimulates TSH and Prolactin secretion Stimulates GH secretion Inhibits GH (and other hormone) secretion Stimulates LH and FSH secretion Stimulates PRL secretion Inhibits PRL secretion

Classification of hormones
There are two classifications of hormones: steroidal and non-steroidal Steroidal hormones are lipid soluble and can diffuse directly into the target cells via the cell membrane. Non-Steroidal hormones are synthesized by amino acids and target cells need receptors to diffuse into the cell.

Classification of hormones
Peptide hormones (Hydrophilic: polar)
formed from chains of amino acids most hormones are peptide hormones longer chains are called protein hormones Example: growth hormone

Steroid hormones (Hydrophobic: nonpolar)

type of lipid derived from cholesterol Example: testosterone

Biogenic amines (Hydrophobic: nonpolar)

small molecules produced by altering the structure of a specific amino acid Example: thyroid hormone

Water and Lipid soluble hormones

Major mechanism of hormone action

Negative feedback Loop

Positive feedback Loop

Negative Feedback Loop

Mechanism:
A stimulus starts a process Process causes release of a hormone Either the hormone or a product of its effects causes the process to slow down or turn off.

Example: the regulation of the blood glucose level in the body

Negative Feedback Loop

Positive Feedback Loop

Called positive because it accelerates the original process
can ensure that the pathway continues to run can speed up its activities.

Few positive feedback loops in the human endocrine system.

Example: milk release from the mammary glands

Positive Feedback Loop

Endocrine Glands

Thyroid gland
Largest pure endocrine gland Internally, composed of hollow follicles
- separated by areolar CT rich in capillaries - walls are formed of cuboidal or squamous epithelial cells (follicular cells) - lying within the epithelium are parafollicular (C) cells - central lumen filled with colloid (gluelike) consisting of thyroglobulin (protein precursor to thyroid hormone)

Amino-based TH and protein based Calcitonin

Thyroid gland

Anatomy and Histological Organization of the Thyroid Gland

Anatomy and Histological Organization of the Thyroid Gland

The Regulation of Thyroid Secretion

Thyroid function is regulated primarily by variations in the circulating level of TSH. TSH secretion is increased by TRH and inhibited in a negative feedback fashion by circulating free T4 and T3. The effect of T4 is enhanced by production of T3 in the cytoplasm of the pituitary cells by the 5'-D2 they contain. TSH secretion is also inhibited by stress, and in experimental animals it is increased by cold and decreased by warmth.

Some of the widespread effects of THs in the body are secondary to stimulation of O2 consumption (calorigenic action). THs also affect growth and development in mammals, help regulate lipid metabolism, and increase the absorption of carbohydrates from the intestine.

They also increase the dissociation of O2 from hemoglobin by increasing red cell 2,3-DPG

Parathyroid glands
Lie on the posterior surface of the thyroid gland surrounded by CT capsules (number varies) Contains thick branching cords composed of 2 types of endocrine cells - chief cells small abundant parathyroid glandular cells that produce PTH - Oxyphil cells and transitional cells likely immature of inactive principal cells Regulates calcium homeostasis: PTH increases calcium levels and is essential to life: 1) stimulates osteoclasts to release calcium from bones 2) decreases secretion of calcium by the kidney 3) activates vit D, which stimulates uptake of Ca by the intestine

Parathyroid glands

Adrenal gland
Paired pyramidal organs on the superior surface of the kidneys highly vascularized 3 groups of 60 small suprarenal arteries supply each gland: - superior suprarenal arteries from the inferior phrenic artery - middle suprarenal arteries from the aorta; - inferior suprarenal arteries from the renal artery Veins - left suprarenal vein drains into the renal vein - right suprarenal vein drains into the inferior vena cava

Adrenal gland

Adrenal gland
Divided into 2 regions:
- Suprarenal cortex Zona Glomerulosa mineralocorticoids Zona Fasciculata glucocorticoids Zona Reticularis androgens - Suprarenal medulla Chromaffin cells produce epinephrine and norephinephrine - modified ganglionic sympathetic neurons - active in the fight, flight, and fright (fight or flight) response - hormones stored in secretory vesicles

Adrenal gland

Adrenal gland
Both basal secretion of glucocorticoids and the increased secretion provoked by stress are dependent upon ACTH from the anterior pituitary. Angiotensin II also stimulates the adrenal cortex, but its effect is mainly on aldosterone secretion. Large doses of a number of other naturally occurring substances, including vasopressin, serotonin, and VIP, are capable of stimulating the adrenal directly, but there is no evidence that these agents play any role in the physiologic regulation of glucocorticoid secretion.

Mechanism of action of ACTH

When ACTH binds to its receptor (R), adenylyl cyclase (AC) is activated via Gs. The resulting increase in cAMP activates protein kinase A, and the kinase phosphorylates cholesteryl ester hydrolase (CEH), increasing its activity. Consequently, more free cholesterol is formed and converted to pregnenolone. Note that in the subsequent steps in steroid biosynthesis, products are shuttled between the mitochondria and the smooth endoplasmic reticulum (SER). Corticosterone is also synthesized and secreted.

Effects of Glucocorticoids
Glucocorticoids:

increase protein catabolism, hepatic glycogenesis and gluconeogenesis.

exert an antiinsulin action in peripheral tissues raise plasma lipid levels and increase ketone body formation but in healthy persons the increase in insulin secretion provoked by the rise in plasma glucose obscures these actions

Effects of Glucocorticoids
Small amounts of glucocorticoids must be present for a number of metabolic reactions to occur, although the glucocorticoids do not produce the reactions by themselves. This effect is called their permissive action. Permissive effects include the requirement for glucocorticoids to be present: for glucagon and catecholamines to exert their calorigenic effects; for catecholamines to exert their lipolytic effects; and for catecholamines to produce pressor responses and bronchodilation.

Effects of Glucocorticoids
Glucocorticoid excess:

exert a significant mineralocorticoid action Hypertension

leads to bone dissolution by decreasing bone formation and increasing bone resorption osteoporosis accelerate the basic electroencephalographic rhythms and produce mental aberrations ranging from increased appetite, insomnia, and euphoria to frank toxic psychoses

Effects of Glucocorticoids

Pharmacological doses of corticoids: inhibit the inflammatory response to tissue injury inhibit ACTH secretion to the point that severe adrenal insufficiency inhibit growth, decrease GH secretion, induce PNMT, and decrease TSH secretion accelerate the maturation of surfactant in the lungs (during fetal life)

Renin Angiotensin System

Renin, an acid protease secreted by the kidneys into the bloodstream, acts in concert with angiotensin-converting enzyme (ACE) to form angiotensin II. It splits the decapeptide angiotensin I from the amino terminal end of angiotensinogen.

Angiotensinogen is synthesized in the liver. Its circulating level is increased by glucocorticoids, thyroid hormones, estrogens, several cytokines, and angiotensin II.
ACE is a dipeptidyl carboxypeptidase that splits off the physiologically inactive angiotensin I, forming the octapeptide angiotensin II

Renin Angiotensin System

Most of the converting enzyme that forms angiotensin II in the circulation is located in endothelial cells. Much of the conversion occurs as the blood passes through the lungs, but conversion also occurs in many other parts of the body.

Angiotensin II produces arteriolar constriction and a rise in systolic and diastolic blood pressure. It is one of the most potent vasoconstrictors known, being 4 to 8 times as active as norepinephrine Angiotensin II also acts directly on the adrenal cortex to increase the secretion of aldosterone, and the renin angiotensin system is a major regulator of aldosterone secretion

Renin Angiotensin System

Pancreas
It is a soft, lobulated organ that stretches obliquely across the posterior abdominal wall in the epigastric region. It is situated behind the stomach and extends from the duodenum to the spleen.

Pancreas
The pancreas is retroperitoneal except for a small part of its tail. It consists of a head, uncinate process, neck, body, and tail.

Pancreas
The superior pancreaticoduodenal artery from gastroduodenal artery and the inferior pancreaticoduodenal artery from superior mesenteric artery bifurcates into anterior and posterior branches, join each other and form anterior and posterior pancreaticoduodenal arcades supplying the pancreatic head and uncinate process

The pancreatic branches of splenic artery also supply the neck, body and tail of the pancreas. The largest of those branches is called arteria pancreatica magna.
A dorsal dorsal or superior pancreatic artery has a dorsal origin in relation to the pancreas; it is usually present, but has a great variability of origin: from the splenic artery (37%), fourth branch of the celiac (33%), superior mesenteric (21%), and less often from the hepatic (8%). It helps to form an inferior or transverse pancreatic artery, which supplies the lower portion of the body

Pancreas

Veins accompany the SPDA and IPDA. The body and neck of the pancreas drain into splenic vein; the head drains into the superior mesenteric and portal veins. Lymph is drained via the splenic, celiac and superior mesenteric lymph

Pancreas
Pancreas contains endocrine and exocrine cells: Exocrine acinar cells, form most of the gland
- secrete a powerful, digestive fluid digestive juice with enzymes into the duodenum; its duct joins the common bile duct

Endocrine cells are contained in spherical bodies

- pancreatic islets or islets of Langerhans - about 1 million scattered among the exocrine cells

Pancreas
Each islet contains 4 major cells Alpha cells glucagon Beta cells insulin Delta cells somatostatin (growth-hormone inhibiting hormone) F cells pancreatic polypeptide (PP)

Hormones of Pancreas

Pancreas
Glucagon raises blood glucose levels. Insulin lowers blood glucose levels. Somatostatin inhibits both glocagon and insulin release. Pancreatic polypeptide inhibits somatostatin secretion, gallbladder contraction and secretion of digestive enzymes by the pancreas.

Glucagon
Hypoglycemia stimulates release of glucagon Glucagon causes hepatocytes to convert glycogen to glucose (glycogenolysis) Hyperglycemia inhibit release of glucagon

Insulin
Insulin allows glucose to diffuse into cells, increases amino acid uptake by cells, and increaes fatty acid uptake by cells.

This facilitates glucose conversion into glycogen (glycogenesis), synthesis of proteins, and synthesis of fatty acids (lipogenesis).

Insulin: Mechanism of Action

Binding of insulin triggers the tyrosine kinase activity of the subunits, producing autophosphorylation of the subunits on tyrosine residues. The autophosphorylation, which is necessary for insulin to exert its biologic effects, triggers phosphorylation of some cytoplasmic proteins and dephosphorylation of others, mostly on serine and threonine residues. Four related insulin receptor substrate (IRS) proteins in cells have been described (IRS - I to IV). IRS-1 has received the most attention, but pathways in addition to IRS-l play important roles in the actions of insulin.

Exposure to increased amounts of insulin leads to down regulation.

Insulin: Mechanism of Action

Effects of Insulin

The physiologic effects of insulin are far-reaching and complex.

Effects of Insulin
Rapid (seconds)
Increased transport of glucose, AA and K into insulin-sensitive cells

Intermediate (minutes)
Stimulation of protein synthesis Inhibition of protein degradation Activation of glycolytic enzimes and glycogen synthase Inhibition of phosphorilase and gluconeogenic enzimes

Delayed (hours)
Increase in mRNA for lipogenic and other enzimes

Effects of Insulin
Glucose enters cells by facilitated diffusion or, in the intestine and kidneys, by secondary active transport with Na+. In muscle, fat and some other tissues, insulin facilitates glucose entry into cells by increasing the number of glucose transporters in the cell membranes.

They differ from and have no homology with the sodium-dependent glucose transporters, SGLT 1 and SGLT 2, responsible for the secondary active transport of glucose out of the intestine and renal tubules, although the SGLTs also have 12 transmembrane domains. Seven different glucose transporters have been characterized. They contain 492-524 amino acid residues, and their affinity for glucose varies. Each transporter appears to have evolved for special tasks.

Effects of Insulin

Effects of Insulin
GLUT 4 is the transporter in muscle and adipose tissue that is stimulated by insulin. A pool of GLUT 4 molecules is maintained in vesicles in the cytoplasm of insulin-sensitive cells. When the insulin receptors of these cells are activated, the vesicles move rapidly to the cell membrane and fuse with it, inserting the transporters into the cell membrane.

Activation of the insulin receptor brings about the movement of the vesicles to the cell membrane by activating phosphoinositol-3 kinase. Insulin also increases the entry of glucose into liver cells, but it does not exert this effect by increasing the number of GLUT 4 transporters. Instead, it induces glucokinase, and this increases the phosphorylation of glucose, so that the intracellular free glucose concentration stays low, facilitating the entry of glucose into the cell.

When insulin action ceases, the transporter-containing patches of membrane are endocytosed, and the vesicles are ready for the next exposure to insulin.

Pancreas

Interactions between Glucagon and Insulin

Starvation

Gonads
Ovaries (female gonads).
Produce steroid hormones.
Estrogens. Progesterone.

Produce inhibin. Produce relaxin.

Testes (male gonads).

Produce testosterone (an androgen). Produce inhibin.

Gonads
Testes:
- Interstitial cells produce androgens (testosterone) promotes production of functional sperm, maintains secretory glands, influences 2nd sexual characteristics, and stimulates muscle growth - Nurse cells (or sustentabular cells) secrete inhibin

Ovaries
- Follicular cells produce estrogens and inhibin - Corpus luteum releases progestins and relaxin

Gonads
Female sex hormones Estrogen and progesterone along with FSH and LH (from the anterior pituitary), regulate the menstrual cycle, maintain pregnancy, and prepare the mammary glands for lactation. Maintain the feminine secondary sex characteristics (larger breasts and hips). Inhibin inhibits secretion of FSH. Relaxin increases the flexibility of the pubic symphisis during pregnancy and helps dilate the cervix during labor and delivery. Male sex hormones Testosterone regulates the production of sperm. maintains secretory glands, and stimulates muscle growth. Stimulates the production of male secondary sex characteristics (beard growth and deepening of the voice).

Pineal
A small endocrine gland attached to the roof of the third ventricle of the brain.

Pineal
Contains neurons, glial cells, and special secretory cells called pinealocytes Secretes melatonin

Production rates rises at night (darkness) and declines during the day
Melatonin contributes to the bodys biological clock. Melatonin slows the maturation of sperm, oocytes, and reproductive organs

Clinical Note - Endocrine Abnormalities

Clinical Implications of Endocrine System

Pour tre subversif, il faut tre subjectif (Frdric Beigbeder)

Adrin