Endocrine System

THE ENDOCRINE SYSTEM Endocrine Glands • Are ductless glands • Consists of cells that produce internal secretions called hormones Hormones are • Chemical messengers • Enter directly into the bloodstream • Regulate and integrate body functions • Play role in body’s metabolism and growth • Cells of endocrine glands secrete hormones into the extracellular fluid • Hormones enter the capillaries through diffusion and secrete directly into the bloodstream (plasma part of the blood) • Through blood circulation, these hormones can be distributed all over our body. Functions of the Endocrine System
Controls the processes involved in movement and physiological equilibrium
Includes all tissues or glands that secrete hormones into the blood
Secretion of most hormones is regulated by a negative feedback system
The number of receptors for a specific hormone can be altered to meet the body’s demand

Figure 1: Human Endocrine system

Endocrine versus Nervous system • Nervous system performs short term crisis management • Endocrine system regulates long term ongoing metabolic • Endocrine communication is carried out by endocrine cells releasing hormones, • Alter metabolic activities of tissues and organs • Target cells • Paracrine communication involves chemical messengers between cells within one tissue. • Autocrine cells act on the same cell that produced them. Figure 2:Mechanism of paracrine and autocrine cells

Chemical Classification of Hormones Lipid soluble hormones

Water soluble hormones

1. Steroid Hormones: 2. Thyroid hormones: T3&T4 3. The gas nitric oxide: NO
Lipid soluble
Diffuse through membranes
Endocrine organs
Adrenal cortex
Ovaries
Testes
Placenta

Amine hormones –NE, Epinephrine and dopamine. Peptide hormones-ADH ,Oxytocin. Protein hormones including : growth cell hormone and insulin The eicosanoid hormones: are derived from arachidonic acid . the two eicosanoids are prostaglandins and leukotrines.

Mechanisms of hormone action 1. Receptors for catecholamine, peptide hormones, eicosanoids are in the cell membranes of target cells • React with specific receptors outside the cell • This triggers an enzyme reaction with lead to the formation of a second messenger cyclic adenine monophosphate (cAMP). • cAMP can produce specific intracellular functions:

• • • • •

Activates cell enzymes Change in membrane permeability Promote protein synthesis Change in cell metabolism Stimulation of cell secretions

2. Thyroid and steroid hormones cross the membrane and bind to receptors in the cytoplasm or nucleus: • Pass through the cell membrane. • Binds to specific receptors • Then enters the nucleus to bind with the cells DNA which then activates certain genes (Direct gene activation). • mRNA is synthesized in the nucleus and enters the cytoplasm and promotes protein synthesis for: • Enzymes as catalysts • Tissue growth and repair • Regulate enzyme function Negative Feedback
Negative feedback is the primary mechanism through which your endocrine system maintains homeostasis
Secretion of a specific hormone s turned on or off by specific physiological changes (similar to a thermostat)
EXAMPLE: plasma glucose levels and insulin response Number of Receptors
Down-regulation: is the decrease of hormone receptors which decreases the sensitivity to that hormone
Up-regulation: is the increase in the number of receptors which causes the cell to be more sensitive to a particular hormone

Pituitary Gland (Master of endocrine gland) The pituitary gland is a pea shaped structure that measures 1-1.5cm (0.5 inch) in diameter and lies in the hypophyseal fossa of the sella turica of the sphenoid bone. It attaches to the hypothalamus by a stalk, the infundibulumand has two functionally separate lobes. The anterior pituitary (anterior lobe ), also called the adenohyphophysis, accounts for about 75% of total weight of the gland. The anterior pituitary consist of two parts in an adult : The pars distalis is the larger portion. The pars tuberalis forms sheath around the infundibulum. The posterior pituitary (posterior lobe ), also called the neurohypophysis consist of two parts: the pars nervosa-the larger bulbar portion , and the infundibulum. Pars intermedia atrophies during human fetal development and ceases to exist as a separate lobe in adult. Anterior Pituitary The anterior pituitary or adenohypophysis secrete hormone that regulate a wide range of bodily activities, from growth to reproduction. Release of anterior pituitary hormone is stimulated by releasing hormone and suppressed by inhibiting hormone from hypothalamus. Figure 3: The Anatomy and Orientation of the Pituitary Gland

The Hypophyseal Portal System

Figure 4: The Hypophyseal Portal System

Hypothalamic hormone reach the anterior pituitary through a portal system .Usually , blood passes from the heart through an artery to a capillary to a vein and back to the heart. In a portal system, blood flows from one capillary network into a portal vein, and then into a secondary capillary network without passing through heart. The name of portal system indicates location of the second capillary network. Superior hypophyseal arteries, branches of internal ceratoid arteries, bring blood into the hypothalamus. At the junction of the median eminence of the hypothalamus and the infundibulum, these arteries divided into a capillary network called the primary plexus of the hypophyseal portal system Near the median eminence and above optic chiasm are clusters of specialized neurons, called neurosecretory cells. of the hypothalamus

Types of anterior pituitary cells: Five types of anterior pituitary cells- somatotrophs, thyrotrophs, gonadotrophs, lactotrophs and corticotrophs-secrete seven hormones Anterior pituitary cells (Hormone) Somatotrophs

Releasing hormone Human growth hormone or somatotropin- growth hormone , also known as somatocrinin

Inhibiting hormone Growth hormone –inhibiting hormone also known as somatostatin.

Thyrotropin releasing hormone Thyrotroph(TSH) Gonadotrophic releasing hormone(GnRH) Gonadotrophs (FSH/LH)

-----Prolactin releasing hormone (PRH) .TRH

Lactotrophs (PRL) Corticotroph (ACTH)

Corticotroph (MSH)

Growth hormone –inhibiting hormone

Prolactin inhibiting hormone (PIH), which is dopamine.

Corticotropin releasing hormone(CRH)

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Corticotropin releasing hormone(CRH)

Dopamine

Figure 5: Feedback control of Endocrine Secretion

Thyroid stimulating hormone (TSH) • Triggers the release of thyroid hormones • Thyrotropin releasing hormone promotes the release of TSH Adrenocorticotropic hormone (ACTH) • Stimulates the release of glucocorticoids by the adrenal gland • Corticotrophin releasing hormone causes the secretion of ACTH

Follicle stimulating hormone (FSH) Stimulates follicle development and estrogen secretion in females and sperm production in males. Leutinizing hormone (LH) Causes ovulation and progestin production in females and androgen production in males. Gonadotropin releasing hormone (GNRH) promotes the secretion of FSH and LH. Prolactin (PH) • Stimulates the development of mammary glands and milk production Growth hormone (hGH or somatotropin) • Stimulates cell growth and replication through release of somatomedins or IGF(Insulin like Growth factor) • Growth-hormone releasing hormone (GH-RH) • Growth-hormone inhibiting hormone (GH-IH) • May be secreted by the pars intermedia during fetal development, early childhood, pregnancy or certain diseases • Stimulates melanocytes to produce melanin Melanocyte stimulating hormone (MSH) • May be secreted by the pars intermedia during fetal development, early childhood, pregnancy or certain diseases • Stimulates melanocytes to produce melanin The posterior lobe of the pituitary gland (neurohypophysis) • Contains axons of hypothalamic nerves • Neurons of the supraoptic nucleus manufacture antidiuretic hormone (ADH) • Decreases the amount of water lost at the kidneys • Elevates blood pressure • Neurons of the paraventricular nucleus manufacture oxytocin • Stimulates contractile cells in mammary glands • Stimulates smooth muscle cells in uterus ADH: is a substance that decreases urine production. ADH causes the kidney to return more water to the blood, thus decreasing urine volume. In the absence of ADH, urine output increases more than tenfold, from the normal 1-2 lit to about 20 liters a day. ADH also decreases the water lost through sweating and causes constriction of arterioles, which increases blood pressure. This hormone’s other name, vasopressin, reflects these effect on blood pressure. Oxytocin: During and after delivery of baby, oxytocin affects two target tissues: the mother uterus and breasts. During delivery oxytocin enhance contraction of smooth muscle cell in the wall of the uterus ; after delivery , it stimulates milk ejection from the mammary gland in response to mechanical stimulus provided by suckling infant .

Thyroid gland The butterfly – shaped thyroid gland is located just inferior to the larynx. It is composed of right and left lateral lobes, one on either side of trachea, that are connected by an isthmus anterior to the trachea. Figure 6 : Thyroid Gland

A small, pyramidal-shaped lobe sometimes extends upward from the isthmus. The normal mass of the thyroid is about 30 g. It is highly vascularised and receives 80-120 ml of blood per min. Microscopic spherical sacs called thyroid follicles makes up the most of thyroid gland. The wall of each follicle consists primarily of cells called follicular cells, most of which extend to the lumen of the follicle. A basement membrane surrounds each follicle. When the follicular cells are inactive, their shape is low cuboidal to squamous, but under the influence of TSH they become active in secretion and ranges from cuboidal to low columnar in shape. The follicular cells produce two hormones: thyroxin (tetraiodothyronin) or T4 because it contains four atoms of iodine, and triiodothyronin or T3, which contains three atoms of iodine.T3 and T4 are also known as thyroid hormones. A few cells called parafollicular cells or C cells lies between follicles. They produce the hormone calcitonin, which helps regulate calcium homeostasis.

Figure 7: Thyroid follicle Action of thyroid hormone: Because most body cells have receptors for thyroid hormone T3 and T4. 1. Thyroid hormone increases BMR (Basal Metabolic Rate), the rate of oxygen consumption under standard or basal condition (awake, at rest and fasting). 2. It stimulate synthesis of additional Na+-K+ pump, which uses large amount of ATP to continually eject Na+ from cytosol into ECF and K+ ion from ECF to cytosol . As cell produces and uses more ATP, more heat is given off, and body temp rises. The phenomenon is called calorigenic effect. 3. In the regulation of metabolism thyroid hormone stimulate protein synthesis and increase the use of glucose and fatty acids for ATP production, 4. The thyroid hormone enhances some action catecholamine because they up regulate β receptors so symptoms of hyperthyroidism include increased heart rate, increased blood pressure. 5. Together with human growth hormone and insulin, thyroid hormone accelerates body growth, growth of nervous and skeletal system. Deficiency of thyroid hormone during fetal development infancy childhood causes several mental retardation and stunted growth. Control of Thyroid hormone secretion: 1. Low blood level of T3 & T4 or low metabolic rate stimulates release of TRH through hypothalamus. 2. TRH carried by hypophyseal portal vein to anterior pituitary to stimulate release of TSH. 3. TSH released into blood stimulates thyroid follicular cells. 4. Thyroid follicle stimulates T3 & T4 release into blood by follicular cell. 5. Elevating the level of T3, inhibiting release of TRH and TSH.

Formation, Storage, and Release of Thyroid hormones: The thyroid gland is the only endocrine gland that stores its secretory product in large quantities. Figure 8: Synthesis and secretion of T3 and T4 occur as follows

Synthesis and secretion of T3 and T4 occur as follows, 1. Iodide trapping: thyroid follicular cells trap iodide ion by actively transporting them from the blood into the cytosol. 2. Synthesis of thyroglobulin: while the follicular cells are trapping iodine, they are also synthesizing thyroglobulin (TGB), a large glycoprotein that is produced in the rough endoplasmic reticulum, modified in Golgi complex, and packaged into secretory vesicles. The vesicles then undergo exocytosis, which release TGB into the lumen of the follicle. 3. Oxidation of Iodine: Some of the amino acid in TGB is tyrosine that will become iodinated. However, -vely charged iodide ions cannot bind to tyrosine until they undergo oxidation (removal of electrons) to iodine. 4.Iodination of tyrosine: As iodine molecule I-2 from, they react with tyrosine that are part of TGB Binding of one iodine atom yields monoiodotyrosine (T1), and second iodination produce diiodotyrosine (T-2).the TGB with attached iodine atoms, a sticky material that accumulates and is stored in the lumen of thyroid follicle, is termed colloid. 5.Coupling of T1-and T2 – during last step of synthesis of thyroid hormone, two T2 molecules joined together to form T-4 or one T1 and one T-2 to form T3. 6.Pinocytosis and digestion of colloid: Droplets of colloid reenter follicular cells by Pinocytosis and merge with lysosomes breaks down TGB, cleaving off molecule T-3and T-4. 7.Secretion of thyroid hormone Because T3 and T4 lipid soluble, they diffuse through plasma membrane into interstitial fluid and then into the blood.T4 is normally secreted in larger quantity than T3.--T3 several times more potent than T4. 8.Transport in the blood: More than 99% of both the T3and T4 combine with transport proteins in the blood mainly TBG.

Calcitonin produced by parafollicular cells of thyroid gland. Calcitonin decreases the level of calcium in the blood by inhibiting the action of osteoclast, the cell that breakdown bone extra cellular matrix. (Miacalcein).

THE PARATHYROID GLANDS

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Figure: 9 Parathyroid gland and it microscopic struture

Parathyroid glands secretes parathyroid hormone. • It is small, pea-shaped glands, located in the neck near the thyroid • It is usually 4 - number can vary. • It regulate the level of calcium in the body (osteoclast activity) and regulates phosphate levels. • It produce parathyroid hormone - ↑ level of calcium in blood • Hypocalcaemia can result if parathyroids are removed or destroyed.

Figure 10: Regulation of Calcitonin and Parathhormone (PTH)

ADRENAL GLAND: The paired adrenal (suprarenal) gland, one of which lies superior to each kidney, has flattened pyramidal shape. In an adult, each adrenal gland is 3-5 cm in height, 2-3 cm width, little less than 1 cm thick, mass of 3.5-5 gm only half its size of birth. During embryonic development, the adrenal glands differentiate into two structurally and functionally distinct regions, a large, peripherally located adrenal cortex, comprising 80-90% of the gland and a small centrally located adrenal medulla. A connective tissue capsule covers the gland. The adrenal cortex produces steroid hormones that are essential for life. Complete loss of adrenocortical hormone leads to death due to dehydration and electrolyte imbalance in a few days to week. Adrenal medulla produces three catecholamine hormones, NE, Epinephrine and small amount of dopamine.

Figure 11: Adrenal gland and its microscopic structure.

Adrenal cortex It is subdivided into three zone each of which secretes different hormones. The outer zone just deep to connective tissue capsule is the zona glomerulosa. Its cell, which is closely packed and arranged in spherical clusters and arched columns secrete hormones called mineralcorticoids because affect mineral homeostasis.

Androgens In both male and female, the adrenal cortex secretes small amounts of week androgens. The major androgens secreted by the adrenal gland are dehydroepiandrosterone (DHEA). After puberty in males, the androgens testosterone is also released in much greater quantity by the testes. In females, however, adrenal androgens play important role. They promote libido (sex drive) and are converted into estrogen. Adrenal androgens also stimulate growth of axillary and pubic hair in boys and girls; contribute to the prepubertal growth spurt.

Adrenal medulla It is modified sympathetic ganglion of ANS. The cell of adrenal medulla secrete hormone. The hormone producing cells, called chromaffin cells. Two major hormones synthesized by the adrenal medulla are epinephrine and norepinephrine. It increases blood flow to vascular organ dilate airways to lungs. Increased blood level of glucose and fatty acids. Glucocorticoids The Glucocorticoids, which regulates metabolism and resistance to stress, include cortisol, corticosterone, and cortisone. Control of glucorticoids secretion occurs via a typical negative feedback system. Low blood levels of glucocorticoids, mainly cortisol, stimulate neurosecretory cells in the hypothalamus, to secrete corticotrophin –releasing hormone (CRH). CRH promotes the release of ACTH from the anterior pituitary. ACTH flows in the blood to adrenal cortex, where it stimulates glucocorticoids secretion. Glucocorticoids have following effect: 1. Protein breakdown: it increases, the rate of protein breakdown, mainly in muscle fibers, and thus increases the liberation of amino acid into the blood stream. 2. Glucose formation: liver cell converts amino acid to glucose. 3. Lipolysis: breakdown of TG and release of fatty acids from adipose tissue. 4. Resistance to stress: They raise B.P. this effect may be advantageous in case of sever blood loss. 5. Anti-inflammatory effect: Glucocorticoids inhibit WBC that participate in inflammatory reponse.Unfortunately glucocorticoids also retards tissue repair. 6. Depression of immune response:-high dose of Glucocorticoids depress immune response. it is useful in organ transplantation.

Pancreatic islets The pancrease is both an endocrine gland and exocrine gland. The pancrease is made up of small clusters of glandular epithelial cells. About 99% of clusters, called acini, constitute the endocrine portion of organ. The cells within acini secrete a mixture of fluid and digestive enzymes called pancreatic juice. The remaining 1% cluster called pancreatic islets (Islet’s of langerhans from the endocrine portion of pancreas )It is a flattened organ that measures about 12.5-15 cm in length , the pancreases is located in the curves of duodenum , the first portion of small intestine . It consists of head, a body and a tail. Figure 12: The Pancrease

Cell types in pancreatic islets: Each pancreatic islets includes four types of hormone secreting cells. • Alpha or A cells: Constitute about 17% of pancreatic islets and secrete glucagon. • Beta or B cells : Constitute about 70% pancreatic islets cells secrete insulin . • Delta cell about 70% of pancreatic islets cells and secrete somatostatin. • F cells: Constitute the remainder of pancreatic islets cells secrete polypeptide • Insulin lowers blood glucose by increasing the rate of glucose uptake and utilization

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Glucagon raises blood glucose by increasing the rates of glycogen breakdown and glucose manufacture by the liver. Figure13: Regulation of insulin and glucagons secretion

Blood glucose level is the most important regulator of insulin and glucagons, several hormones and neurotransmitter also regulates the release of these two hormones. Insulin secretion is also stimulated by, • Acetylcholine, the neurotransmitter liberated from axon terminals of parasympathetic vagus nerves fiber that innervate pancreatic islets. • The amino acids arginine and leucine , which would be present in blood at higher levels after protein containing meal. • Glucose dependent insulinotropic peptide (GIP) a hormone released by enteroendocrine cells of small intestine in response to the presence of glucose in the gastrointestinal tract. Digestion and absorption of food containing both carbohydrate and protein provide strong stimulation for insulin release. Glucagon secretion is stimulated by, Increased activity of the sympathetic division of the ANS , as occurs during exercise. A raised in blood amino acids , if blood glucose level is low , which could occur after a meal that contained mainly protein. Ovaries and Testes Gonads are the organs that produce gametes, sperm in males, oocyte in females. Ovaries , paired oval bodies located in the female pelvic cavity , produce several steroidhormones, including two estrogens (estradiol and estrol) and progesterone.

Theses female sex hormones, along with FSH and LH from the anterior pituitary, regulates the menstrual cycle, maintain pregnancy and prepare the mammary gland for lactation. They also provide enlargement of breast and widening of hips at puberty and help maintain these female secondary sex characteristics. The ovaries also produce inhibin, a protein hormone that inhibit secretion of FSH. During preganancy , the ovaries and placenta produce a peptide hormone called relaxin Relaxin increases the flexibility of pubic symphisis during pregnancy and helps dilate the uterine cervix during labor and delivery. Male Gonads The testes are oval glands that lie in the scrotum. The main hormone produced and secreted by the testes is testosterone, an androgen or male sex hormone. Testesterone develops and regulates sperm and stimulates the developments and maintainance of male secondary sex characteristics, such as beard growth, deepening of voice. Testes also produce inhibin, which inhibits secretion of FSH. Pineal gland It is a small endocrine gland that attached to the roof of third ventricle of the brain at the midline . Part of the epithalamus , it is position between the two superior colliculi. It has a mass 0.1-0.2 g and is covered by capsule formed by the pia matter. The gland consists of masses of neuroglia and secretory cells called pinealocytes. Pineal gland secrete melatonin , an amine hormone derived from serotonin, and that more melatonin is released in darkness and less in strong sunlight. In darkness, norepinephrine released by the sympathetic fibers, stimulates, synthesis and secretion of melatonin which promote sleepiness. Melatonin is thought to contribute to setting the body’s biological clock, which is controlled from the suprachiasmatic nucleus of the hypothalamus. During sleep melatonin level is increased tenfold and then decline to a low level again before awakening. Melatonin is also potent antioxidant that may provide some protection against damaging oxygen free radicals. Thymus It is located behind the sternum between the lungs.the hormone produced by the thymus,-thymosin, thymic humoral factor(THF), thymic factor(TF) and thymopoietin promote maturation of T-cells and may retard aging process.` .