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1 Anatomy & Physiology II Chapter 17(The Endocrine System) The Endocrine System works with the Nervous System to coordinate body’s functions. -Endocrine & Nervous Systems may excite or inhibit each other. COMPARISON OF THE ENDOCRINE AND NERVOUS SYSTEMS: Mediator: Effect: Response: Action: Endocrine System Nervous System Chemical messengers. (hormones) Longer More Generalized Slower Electrical impulses Shorter More Localized Rapid Hormones have an effect on: Smooth & Cardiac muscles Glands Metabolism Growth & development Reproduction Homeostasis etc. Endocrinology is the study of endocrine glands and the management of its’ diseases COMPARISON OF THE EXOCRINE AND ENDOCRINE GLANDS: Exocrine glands Endocrine glands Have ducts Produce secretions Secretions released in organs, cavities or on the surface Usually local action Ductless glands Produce hormones Secretion released into the blood Act on hormone receptors Include: -Sweat -Sebaceous, Mucous -Mammary -Digestive (enzymes) Include: -Pituitary & Pineal glands -Thyroid & Parathyroids -Adrenals -Gonads(testes, ovaries) Some non-endocrine organs that contain cells producing hormones include: Hypothalamus Thymus Pancreas Stomach, Liver, small intestine Kidneys, heart, placenta Skin & Adipose tissue 2 Circulating hormones act on specific protein receptors on a target cell (TSH acts on thyroid cells) -They are inactivated by the liver and excreted by the kidneys. Local hormones act locally on the cells nearby, without entering blood. -They are inactivated quickly. HORMONE CHEMISTRY: 1. Fat Soluble Hormones– a) Steroid hormones – Derived from cholesterol (Cortisol, Estrogen, Testosterone) b) Thyroid hormones – Derived from amino acid tyrosine and iodine (T3 and T4) c) Gas – Nitric oxide Functions as a hormone & a neurotransmitter 2. Water Soluble Hormones – a) b) c) d) Amine hormones – Derived by modifying amino acids (Epinephrine, NE, Melatonin, Histamine) Peptides hormones – Derived from small (<50) amino acid chains (ADH, oxytocin) Proteins hormones - Derived from larger (50-200) amino acid chains (HGH, Insulin, Gastrin) Eicosanoid hormones – Derived from 20-carbon fatty acids (Prostaglandins, Leukotrines) MECHANISMS OF HORMONE ACTION: The same hormone may have a different effect on different target cells. -For example, insulin stimulates liver cells to produce glycogen & fat cells to produce triglycerides. Hormone effects depend upon the permeability of the plasma membrane. They include: Stimulating transport of substances in or out of cells (insulin causes glucose to enter cells) Alter rate of metabolism (Thyroxine increases metabolic rate) Contract or relax smooth or cardiac muscles (epinephrine increases cardiac muscle contraction) Action of lipid-soluble hormones – 1. 2. 3. 4. 5. 6. Lipid soluble hormone detaches from its’ transporting protein molecule in the blood Free hormone passes through the lipid bi-layer of plasma membrane It binds to its’ receptor inside the target cell Hormone-receptor complex turns some genes off and other genes on New proteins (usually enzymes) are produced in response to this gene alteration New enzymes alter cell function Action of water-soluble hormones – 1. Water soluble hormone (first messenger) binds to its’ receptor on the target cell membrane. 2. ATP in the cell cytosol converts to cyclic AMP (second messenger) 3. Cyclic AMP activates enzymes inside the cell and then inactivates itself 3 CONTROL OF HORMONE SECRETIONS: Hormones are secreted intermittently in response to stimulation of the endocrine gland. Hormone secretion is controlled by: Nervous System (Axons from the hypothalamus regulate pituitary gland) Chemical changes in the blood (Increased glucose level increases insulin secretion) Other hormones (Thyroid stimulating hormone from the pituitary controls thyroid secretions) Most hormone controls occur via negative feedback (↑ hormone levels leads to ↓ hormone secretion) Some hormone controls occur via positive feedback (oxytocin in childbirth & lactation) HYPOTHALAMUS & PITUITARY GLAND Hypothalamus & Pituitary gland produce hormones that control all the other endocrine glands. Pituitary gland (hypophysis) is about 1 cm in diameter (pea size). -It rests in the sella turcica, a depression in the sphenoid bone -It is connected to the hypothalamus via the infundibulum -Pituitary gland is divided into two lobes: 1. Anterior lobe (adenohypophysis) 2. Posterior lobe (neurohypophysis) Hypophyseal portal veins connect capillaries of the hypothalamus and anterior lobe of pituitary. Neurosecretory cells of the hypothalamus release their hormones into the hypothalamic capillaries. -Their axons also extend into the posterior lobe, where they release hormones (Oxytocin, ADH) ANTERIOR PITUITARY HORMONES – Releasing & inhibiting hormones produced in the hypothalamus regulate hormone production in the anterior pituitary gland. They reach the anterior pituitary directly via the hypophyseal portal veins. Tropic hormones (Tropins) are produced by the anterior pituitary. 4 Tropins control other endocrine glands. They include: 1. Human Growth hormone (hGH) –Regulate body growth & metabolism 2. Thyroid Stimulating hormone (TSH) – Stimulates thyroid secretions 3. Follicle Stimulating hormone (FSH) – Stimulates sperm, ovum & estrogen production 4. Leutinizing hormone (LH) – Stimulates secretion of testosterone, estrogen & progesterone - Triggers ovulation 5. Prolactin (PRL) – Stimulates milk secretion. 6. Adrenocorticotrophic hormone (ACTH) – Stimulates secretion of hormones by adrenal cortex 7. Melanocyte Stimulating hormone (MSH) – Stimulates melanocytes to produce more melanin 1. Human Growth Hormone (hGH) & Insulin-like Growth Factors (IGFs)– Human Growth Hormone is the most abundant anterior pituitary hormone. Hypothalamus controls the secretion of hGH by 2 hormones: Growth Hormone Releasing Hormone (GHRH) - increases hGH secretion Growth Hormone Inhibiting Hormone (GHIH) - decreases hGH secretion Hypoglycemia stimulates release of GHRH. Hyperglycemia stimulates release of GHIH. Human Growth Hormone is secreted in bursts every few hours, specially when one is asleep. hGH stimulates secretion of Insulin-like Growth Factors by the liver, bone, muscle & cartilage. hGH and IGFs regulate body’s growth, metabolism & repair. -Like insulin, IGFs increase the rate of protein synthesis and size & numbers of cells (bone, muscle etc) -IGFs also increase glycogen and fat breakdown to produce ATP. 2. Thyroid Stimulating hormone (TSH) – Thyrotropic Releasing Hormone (TRH) from the hypothalamus controls the secretion of TSH. TSH controls the secretion of thyroid hormones T3 and T4. All these hormones are controlled by a negative feedback mechanism. 3. Follicle Stimulating hormone (FSH) – FSH Releasing Hormone from hypothalamus controls the release of FSH. A negative feedback mechanism controls the release of FSH and its’ releasing hormone. FSH matures sperms and oocytes and stimulates estrogen production in females. 5 5. Luteinizing Hormone (LH) – LH Releasing Hormone from hypothalamus controls the release of LH. It stimulates secretion of testosterone, estrogens, progesterone and triggers ovulation. -Estrogen and progesterone prepare the uterus for ovum implantation and the breast for lactation. 6. Prolactin (PRL) – Prolactin Releasing & Inhibiting Hormones secreted by the hypothalamus control prolactin secretion. Prolactin works with estrogen & progesterone to secrete milk from the female mammary glands. Prolactin levels rise just before menstruation, during pregnancy and while nursing a baby. In males, hypersecretion of prolactin causes impotence. 7. Adrenocorticotropic Hormone (ACTH) – ACTH Releasing Hormone from the hypothalamus & stress stimulate the secretion of ACTH. ACTH stimulates the release of glucocorticoids from the adrenal cortex. Increased glucocorticoid level decreases the secretion of ACTH and ACTH Releasing hormone POSTERIOR PITUITARY HORMONES – Posterior pituitary only stores & releases two hormones produced in the hypothalamus: Oxytocin (OT) Antidiuretic Hormone (ADH) Nerve impulses release these hormones from storage in the axon terminals of the posterior pituitary. Oxytocin It contracts uterus after delivery and stimulates milk ejection in response to suckling reflex. It may also be responsible for sexual pleasure of coitus and parenting behavior towards offspring. Antidiuretic hormone (ADH, Vasopressin) – It prevents water loss from the body by decreasing urine volume and reducing sweating It also causes constriction of arterioles (vasoconstriction) and thereby, increases blood pressure. Hyposecretion of ADH or lack of ADH receptors causes Diabetes Insipidus (excessive water loss) 6 Amount of ADH secretion depends on blood osmotic pressure and blood volume as follows: 1. Decreased blood volume (dehydration, diarrhea, hemorrhage) or increased osmotic pressure of blood stimulates osmoreceptors in the hypothalamus 2. Osmoreceptors activate neurosecretory cells in the hypothalamus to release ADH 3. Blood carries ADH to: Kidneys - which retain water & urine volume Sweat glands - which reduce sweating Smooth muscle in blood vessel walls - which cause vasoconstriction & increase blood pressure 1. Increased blood volume (overhydration) or decreased osmotic pressure inhibits osmoreceptors. 2. Inhibition of osmoreceptors inhibits ADH secretion by hypothalamus. 3. Decreased ADH secretion increases water loss in urine, sweat and causes vasodilatation (↓BP) ADH secretion increases due to: Trauma and Pain Stress Drugs – nicotine, morphine, tranquilizers, anesthetics increase ADH secretion - Alcohol inhibits ADH secretion (causes diuresis, dehydration and ‘hangover’) THYROID GLAND This butterfly-shaped gland is situated below the Adam’s apple in the anterior neck. Its’ right and left lobes are connected by a bridge (isthmus) in front of the trachea. Follicles are sac-like structures all over the thyroid. Follicular cells line the follicles. Follicular cells produce thyroid hormones T3 (triiodothyronine) and T4 (thyroxine) Thyroid hormones are stored in the follicles until body needs them. T4 is converted in the body’s cells to T3 before being utilized. Fewer parafollicular cells lie between the follicles and produce hormone calcitonin. Hyperthyroidism means increased thyroid hormone secretion. -It causes tachycardia, hypertension, nervousness, tremors, weight loss etc. 7 Actions of thyroid hormones – Thyroid hormones affect most body cells as they have receptors for them. Thyroid hormones: Increase Basal Metabolic Rate (BMR) Increase Oxygen utilization Increase body temperature Increase protein synthesis (stimulating body growth) Increase glucose utilization to produce energy (ATP) Increase lipolysis (fat breakdown) Increase cholesterol excretion by the body (reducing blood choleasterol) Regulation of thyroid hormones– 1. Decreased T3, T4 level (or decreased metabolic rate) increases TRH secretion from hypothalamus 2. Increased TRH level stimulates TSH secretion from the anterior pituitary 3. Increased TSH level stimulates secretion of T3, T4 from the follicular cells of thyroid 4. Increased T3, T4 levels inhibit TRH and TSH secretion (negative feedback) Thyroid secretion increases in cold temperature, pregnancy, hypoglycemia and at high altitudes. Thyroid secretion decreases when iodine levels are very high. Calcitonin (CT)– Calcitonin inhibits the breakdown of bone by osctoeclasts. It increases deposition of calcium and phosphorus in the bone -Calcitonin actions reduce blood calcium levels PARATHYROID GLANDS There are 4 parathyroid glands – Right Superior & Inferior and Left Superior & Inferior. -They are situated on the back of the thyroid gland. They have principal cells that produce Parathyroid Hormone (PTH). Negative feedback, depending on blood Ca++ level, operates as follows: 1. Increased blood Ca++ level increases calcitonin secretion from the thyroid gland. 2. Calcitonin moves Ca++ into the bone, reducing blood Ca++ levels 8 3. Reduced blood Ca++ level stimulates PTH secretion from the parathyroid glands 4. PTH increases Ca++ absorption from bones and decreases their loss in urine - PTH also stimulates kidneys to secrete calcitriol, which increases Ca++ absorption in the gut. 5. Blood Ca++ level increases. ADRENAL GLANDS An adrenal gland is situated superior to each kidney (suprarenal gland) Its’ outer part is called adrenal cortex (80% of gland) Its’ inner part is called adrenal medulla. Adrenal cortex is further divided into outer, middle & inner zones secreting different hormones: MINERALOCORTICOIDS (produced in outer zone) The main hormone aldosterone reabsorbs Na+ and H2O from urine and excretes K+ in urine. Aldosterone operates by the Renin-angiotensin-aldosterone pathway: 1. Reduced blood volume & BP occur due to reduced blood Na+ level (dehydration, hemorrhage) 2. Low BP stimulates renin secretion in kidneys 3. Renin converts angiotensinogen to angiotensin I 4. Angiotensin converting enzyme (ACE) in the lungs converts angiotensin I to angiotensin II. 5. Angiotensin II causes vasoconstriction & stimulates aldosterone secretion in adrenal cortex. 6. Aldosterone increases Na+ and H2O reabsorption & K+ excretion in kidneys 7. This increases blood volume & BP. GLUCOCORTICOIDS (produced in middle zone) – The main hormone cortisol has the following functions: 1. Proteolysis – Breakdown of proteins to amino acids. 2. Glucogenesis – Makes glucose from amino acids or lactic acid 3. Lipolysis – Breaks down triglycerides into fatty acids 4. Increases resistance to stress (disease, trauma, surgery etc) 9 5. Anti-inflammatory action – Inhibit leukocytes, slow tissue repair and depress immune response Glucocorticoids are controlled by negative feedback mechanism: ↓ Glucocorticoid level (STRESS) ↑ ACTH releasing hormone (hypothalamus) ↑ ACTH (ant pituitary) ↑ blood Glucocorticoid secretion (adrenal cortex) ANDROGENS (produced in inner zone) – Small amounts of these male sex hormones are secreted by adrenal cortex in both males & females Their function is: Maintain libido (sex drive) Stimulate prepubertal growth spurt Stimulate secondary sexual characters (hair growth etc) Androgen secretion is controlled by ACTH secretion from the anterior pituitary. Adrenal medulla consists of sympathetic post-ganglionic fibers of the autonomic nervous system. It is controlled directly by stimulation from the hypothalamus in response to stress and hypoglycemia. It secretes two hormones – Epinephrine & Norepinephrine. -They help body in the flight-of-fight response and resist stress. -Their effects include ↑ heart rate & BP Vasodilatation Bronchodilation Hyperglycemia Hyperlipemia PANCREAS It is located posterio-inferior to the stomach in the duodenal curve It has clusters of cells (islets of Langerhans) containing 4 types of cells: 1. Alpha cells - secrete hormone glucagon 2. Beta cells - secrete hormone insulin 3. Delta cells – secrete somatostatin (inhibits insulin & glucagon secretion) 4. F cells – secrete pancreatic polypeptide (regulates pancreatic enzymes) 10 GLUCAGON – Increases blood glucose level by: Breakdown of glycogen to glucose Formation of glucose from amino acids & lactic acid Glucose release from liver into blood Sympathetic simulation or hypoglycemia increased glucagon secretion. Parasympathetic stimulation or hyperglycemia reduced glucagon secretion. INSULIN – Decreases blood glucose level by: Pushing glucose into body cells (skeletal muscles) Increasing Glycogen and fatty acid synthesis from glucose Increasing protein formation from amino acids Inhibiting glycogen breakdown Inhibiting glucose formation in the liver Hyperglycemia increased insulin secretion Hypoglycemia inhibits insulin secretion OVARIES & TESTES OVARIES are two almond-size female gonads in the pelvic cavity They secrete: Steroid hormones estrogen & progesterone and Protein hormones inhibin & relaxin. Along with anterior pituitary hormones, estrogen & progesterone are responsible for: Female sexual characters Menstrual cycle Maintenance of pregnancy Lactation Inhibin inhibits the secretion of FSH from anterior pituitary (during pregnancy & lactation) Relaxin relaxes the cervix and ligaments at pubic symphysis (during labor) TESTES are two male gonads in the scrotal sac. They produce hormones testosterone and inhibin. Testosterone regulates spermatogenesis and secondary male sex characters. Inhibin inhibits the secretion of FSH from anterior pituitary 11 Abuse of anabolic steroid hormones causes: Heart, kidney and liver damage Mood swings & aggressive behavior Masculinization of females (breast & uterus atrophy, irregular menses, hair growth, deep voice) Testicular atrophy and baldness in males PINEAL GLAND This small, pinecone-shaped gland is situated at the roof of the 3rd ventricle in the brain. It secretes hormone melatonin, which regulates biorhythms - sleep and wakefulness More melatonin is produced by the pineal gland in darkness Melatonin overproduction during long winter nights causes depression (seasonal affective disorder) THYMUS It is located posterior to the upper sternum in young children. It produces hormones thymosin, thymic humoral factor (THF), thymic factor (TF) and thymopoetin. -They help T-cell (leukocytes responsible for protection) maturation & may retard aging process Other Endocrine Tissues Gastrointestinal tract – Gastrin - Secretes gastric juice, increases stomach motility Glucose-dependent Insulnotropic Peptide (GIP) – Stimulates insulin secretion by pancreas Secretin – Stimulates bile and pancreatic juice secretion Cholecystokinin - Stimulates bile and pancreatic juice secretion & causes stomach fullness after meals Placenta – Human Chorionic Gonadotrophin (HCG) – Stimulates estrogen & progesterone in pregnancy Kidneys – Erythropoetin (EPO) – Increases RBC production Heart – Atrial Natriuretic peptide (ANP) – Secreted by atria, it ↓ BP. Adipose tissue – Leptin – Suppresses appetite EICOSANOIDS These include local hormones prostaglandins (PGs) and Leukotrines (LTs) 12 All the cells in the body secrete them (except red blood cells) 1. Prostaglandins intensify pain, inflammation & promote fever. -They influence smooth muscle contraction, gland secretions, blood flow, nerve conduction & platelet function. Aspirin & NSAIDS (motrin) inhibit prostaglandin synthesis and, thereby, reduce inflammation. 2. Leukotrines stimulate leukocyte movement in inflammation. STRESS RESPONSE Eustress is healthy stress essential in life. Distress or unhealthy stress is harmful to life. A Stressor is a simulus (heat, cold, toxin, hemorrhage, emotion) that produces a stress response. Stress response or general adaptation syndrome (GAS) is the body changes in response to a stressor. There are 3 stages of stress response: 1. Flight-or-Flight Reponse – This short-term first stage prepares us to run from or fight a stressor It is controlled by sympathetic nerve impulses from the hypothalamus. 2. Resistance Reaction – this longer-term second stage is controlled by releasing hormones from hypothalamus. It helps us continue fighting the stress and repair the damage to the body. If this stage fails our body enters the: 3. Exhaustion stage – The body resources are depleted during the first two stages. This causes muscle wasting, immune suppression, GIT ulcecration & failure of insulin production. The body is susceptible to diseases like cancer, HPT, diabetes, stroke, MI, depression, colitis etc. -X-