Chapter 18 The Endocrine System

1. Chapter 18The Endocrine System • Endocrine and nervous systems work together • Endocrine system • hormones released into the bloodstream travel throughout the body • results may take hours, but last longer • Nervous system • certain parts release hormones into blood • rest releases neurotransmitters excite or inhibit nerve, muscle & gland cells • results in milliseconds, brief duration of effects

2. General Functions of Hormones • Help regulate: • extracellular fluid • metabolism • biological clock • contraction of cardiac & smooth muscle • glandular secretion • some immune functions • Growth & development • Reproduction

3. Endocrine Glands Defined • Exocrine glands • secrete products into ducts which empty into body cavities or body surface • sweat, oil, mucous, & digestive glands • Endocrine glands • secrete products (hormones) into bloodstream • pituitary, thyroid, parathyroid, adrenal, pineal • other organs secrete hormones as a 2nd function • hypothalamus, thymus, pancreas,ovaries,testes, kidneys, stomach, liver, small intestine, skin, heart & placenta

4. Hormone Receptors • Hormones only affect target cells with specific membrane proteins called receptors

5. Circulating & Local Hormones • Circulating hormones • act on distant targets • travel in blood • Local hormones • paracrines act on neighboring cells • autocrines act on same cell that secreted them

6. Lipid-soluble Hormones • Steroids • lipids derived from cholesterol on SER • different functional groups attached to core of structure provide uniqueness • Thyroid hormones • tyrosine ring plus attached iodines are lipid-soluble • Nitric oxide is gas

7. Water-soluble Hormones • Amine, peptide and protein hormones • modified amino acids or amino acids put together • serotonin, melatonin, histamine, epinephrine • some glycoproteins • Eicosanoids • derived from arachidonic acid (fatty acid) • prostaglandins or leukotrienes

8. Hormone diffuses through phospholipid bilayer & into cell Binds to receptor turning on/off specific genes New mRNA is formed & directs synthesis of new proteins New protein alters cell’s activity Action of Lipid-Soluble Hormones

9. Action of Water-Soluble Hormones • Can not diffuse through plasma membrane • Hormone receptors are integral membrane proteins • act as first messenger • Receptor protein activates G-protein in membrane • G-protein activates adenylate cyclase to convert ATP to cAMP in the cytosol • Cyclic AMP is the 2nd messenger • Activates kinases in the cytosol to speed up/slow down physiological responses • Phosphodiesterase inactivates cAMP quickly • Cell response is turned off unless new hormone molecules arrive

10. Hormonal Interactions • Synergistic effect • a second hormone, strengthens the effects of the first • two hormones acting together for greater effect • thyroid strengthens epinephrine’s effect upon lipolysis • Permissive effect • you need two hormone present for one hormone to work properly • estrogen & LH are both needed for oocyte production • Antagonistic effects • two hormones with opposite effects • insulin promotes glycogen formation & glucagon stimulates glycogen breakdown

11. Control of Hormone Secretion • Regulated by signals from nervous system, chemical changes in the blood or by other hormones • Negative feedback control (most common) • decrease/increase in blood level is reversed • Positive feedback control • the change produced by the hormone causes more hormone to be released • Disorders involve either hyposecretion or hypersecretion of a hormone

12. Hypothalamus and Pituitary Gland • Both are master endocrine glands since their hormones control other endocrine glands • Hypothalamus is a section of brain above where pituitary gland is suspended from stalk • Hypothalamus receives input from cortex, thalamus, limbic system & internal organs • Hypothalamus controls pituitary gland with 9 different releasing & inhibiting hormones

13. Hormones: human growth hormone- hGH thyroid stimulating - TSH follicle stimulating- FSH leutinizing hormone - LH prolactin adrenocorticotropin - ACTH melanocyte stimulating - MSH Pituitary Gland 5 types of cells: • somatotrophs: secrete hGH/somatotropin • thyrotrophs: secrete TSH/thyrotropin • gonadotrophs: secrete FSH, LH • lactotrophs: secrete prolactin • corticotrophs: secrete ACTH/corticotropin & MSH • Pea-shaped, 1/2 inch gland found in sella turcica of sphenoid • Infundibulum attaches it to brain • Anterior lobe = 75% develops from roof of mouth • Posterior lobe = 25% • ends of axons of 10,000 neurons found in hypothalamus • neuroglial cells called pituicytes

14. Human Growth Hormone • Produced by somatotrophs • induces target cells to make insulin-like growth factors (IGFs) that act locally or enter bloodstream • common target cells of IGFs are liver, skeletal muscle, cartilage and bone • GH + IGFs increase cell growth & cell division by increasing their uptake of amino acids & synthesis of proteins • stimulate lipolysis in adipose so fatty acids used for ATP • retard use of glucose for ATP production by cells • reduces uptake of glucose by the liver and promote breakdown of liver glycogen– so blood glucose levels stay high enough to supply brain • Excess of growth hormone • raises blood glucose concentration • pancreas releases insulin continually • Leads to beta-cell burnout • Diabetogenic effect • causes diabetes mellitis if no insulin activity can occur eventually

15. Regulation of hGH • Low blood sugar stimulates release of GNRH from hypothalamus • anterior pituitary releases more hGH, more glycogen broken down into glucose by liver cells • High blood sugar stimulates release of GHIH from hypothalamus • less hGH from anterior pituitary, glycogen does not breakdown into glucose

16. Thyroid Stimulating Hormone (TSH) • Hypothalamus regulates thyrotroph cells • Thyrotroph cells produce TSH • TSH stimulates the synthesis & secretion of T3 and T4 • Metabolic rate stimulated

17. Thyroid Gland • comprised of microscopic sacs called follicles = follicular cells making up the walls, surrounds a lumen • synthesize T3 & T4 (thyroxin) • In between follicular cells cells are parafollicular cells • produce calcitonin • On each side of trachea is lobe of thyroid • connected by an isthmus • Weighs 1 oz & has rich blood supply

18. Formation of Thyroid Hormone • Iodide trapping: follicular cells actively take up iodine from blood • Synthesis of thyroglobulin (TGB): follicular cells make TGB - secreted into the follicle lumen as the material colloid • Iodination of colloid: iodine ions are oxidated (I2- -> I2) by peroxidase within the cell • oxidized iodine then binds onto tyrosine residues on the TGB within colloid • Coupling of T1 and T2: forms T3 & T4 • Uptake of colloid by follicular cells: digestion cleaves off T3 and T4 • Secretion of T3 & T4 into blood: T3 & T4 are transported in blood bound to thryoxine-binding globulin

19. Actions of Thyroid Hormones • T3 & T4 = increases metabolic rate stimulates synthesis of protein stimulates breakdown of fats stimulates cholesterol excretion increases use of glucose & oxygen (ATP production) increases body temperature (calorigenic effect)

20. Control of T3 & T4 Secretion • Low blood levels of hormones stimulate hypothalamus -> TRH • It stimulates pituitary to release TSH • TSH stimulates gland to raise blood levels • T3 and T4 regulate themselves through a negative feedback loop

21. Parathyroid Glands • 4 pea-sized glands found on back of thyroid gland • Principal cells produce parathyroid hormone (PTH) • Oxyphil cell function is unknown

22. Parathyroid Hormone • Raises blood calcium levels • increases activity of osteoclasts (bone degrading cells) • increases reabsorption of Ca+2 by kidney • promote formation of calcitriol (vitamin D3) by kidney which increases absorption of Ca+2 and Mg+2 by intestinal tract • Opposite function of calcitonin (thyroid) • High or low blood levels of Ca+2 stimulate the release of different hormones --- PTH or CT • high level of calcium in blood - release of calcitonin by parafollicular cells, promotes uptake of calcium into bone matrix, lowers blood calcium • low level of calcium in blood - release of PTH by parathyroid glands, promotes release of calcium from bone, raises blood calcium

23. Follicle Stimulating Hormone (FSH) • Releasing hormone from hypothalamus controls gonadotrophs • Gonadotrophs release follicle stimulating hormone • FSH functions • initiates the formation of follicles within the ovary • stimulates follicle cells to secrete estrogen • stimulates sperm production in testes

24. Luteinizing Hormone (LH) • Releasing hormones from hypothalamus stimulate gonadotrophs • Gonadotrophs produce LH • In females, LH stimulates • secretion of estrogen • ovulation of 2nd oocyte from ovary • formation of corpus luteum • secretion of progesterone • In males, stimulates interstitial cells to secrete testosterone

25. Ovaries and Testes • Ovaries • estrogen, progesterone, relaxin & inhibin • regulate reproductive cycle, maintain pregnancy & prepare mammary glands for lactation • Testes • produce testosterone • regulate sperm production & 2nd sexual characteristics

26. Prolactin (PRL) • Hypothalamus regulates lactotroph cells • Lactotrophs produce prolactin • Under right conditions, prolactin causes milk production • Suckling reduces levels of hypothalamic inhibition and prolactin levels rise along with milk production • Nursing ceases & milk production slows

27. Melanocyte-Stimulating Hormone • Secreted by corticotroph cells • Releasing hormone from hypothalamus increases its release from the anterior pituitary • Function not certain in humans (increase skin pigmentation) • May have a role in promoting sexual performance

28. Adrenocorticotrophic Hormone • Hypothalamus releasing hormones stimulate corticotrophs • Corticotrophs secrete ACTH (& MSH also) • ACTH stimulates cells of the adrenal cortex

29. Adrenal Glands • Cortex derived from mesoderm • Medulla derived from ectoderm • One on top of each kidney • 3 x 3 x 1 cm in size and weighs 5 grams • Cortex produces 3 different types of hormones from 3 zones of cortex: mineralcorticoids (aldosterone), glucocorticoids (cortisol) & androgens • Medulla produces epinephrine & norepinephrine

30. AdrenalGland • Cortex • 3 zones • Medulla

31. Mineralocorticoids • 95% of these hormones - aldosterone • Functions • increase reabsorption of Na+ with Cl- , bicarbonate and water following it • promotes excretion of K+ and H+ • dehydration, hemorrhage (decrease in blood volume) - decreases blood pressure - secretion of renin from kidneys which stimulates angiotensin II release from lungs - stimulates aldosterone release from adrenal cortex - increases water uptake from kidneys and increased excretion of K+ into urine

32. Glucocorticoids • 95% of hormonal activity is due to cortisol • neurosecretory cells secrete corticotropin-releasing hormone (CRH) • CRH promotes the release of ACTH where it stimulates the adrenal cortex to secrete corticol • Functions = helps regulate metabolism • increases rate of protein synthesis • increases conversion of amino acids to glucose – energy for protein synthesis • stimulates lipolysis for glucose synthesis (for energy) • increases glucose synthesis – ATP production provides resistance to stress by making nutrients available for ATP • raises BP by vasoconstriction (decreases blood loss) • anti-inflammatory effects reduced (skin cream) • reduces release of histamine from mast cells • decreases capillary permeability • depresses phagocytosis

33. Androgens • Small amount of male hormone produced by the zona reticularis • insignificant in males • may contribute to sex drive in females • is converted to estrogen in postmenopausal females

34. Adrenal Medulla • hormone producing cells = Chromaffin cells receive direct innervation from sympathetic nervous system • Produce epinephrine & norepinephrine • Hormones are sympathomimetic • effects mimic those produced by sympathetic NS • cause fight-flight behavior • sympathetic preganglionic neurons secrete acetylcholine - which stimulates secretion by the AM

35. Posterior Pituitary Gland (Neurohypophysis) • Does not synthesize hormones • Consists of axon terminals of hypothalamic neurons • Neurons release two neurotransmitters that enter capillaries • antidiuretic hormone • oxytocin

36. Oxytocin • Two target tissues both involved in neuroendocrine reflexes • During delivery • baby’s head stretches cervix • hormone release enhances uterine muscle contraction • baby & placenta are delivered • After delivery • suckling & hearing baby’s cry stimulates milk ejection • hormone causes muscle contraction & milk ejection

37. Antidiuretic Hormone (ADH) • Known as vasopressin • Functions • decrease urine production • decrease sweating • increase BP • Dehydration • ADH released • Overhydration • ADH inhibited

38. Pancreas • Organ (5 inches) consists of head, body & tail • Cells (99%) in acini produce digestive enzymes • Endocrine cells in pancreatic islets produce hormones • Exocrine acinar cells surround a small duct = digestive enzymes

39. 1 to 2 million pancreatic islets • Contains 4 types of endocrine cells • Endocrine cells secrete near a capillary • Alpha cells (20%) produce glucagon • Beta cells (70%) produce insulin • Delta cells (5%) produce somatostatin • F cells produce pancreatic polypeptide

40. Regulation of Glucagon & Insulin Secretion • Low blood glucose stimulates release of glucagon • High blood glucose stimulates secretion of insulin

41. Melatonin secretion produces sleepiness - occurs during darkness due to lack of stimulation from sympathetic ganglion Pineal Gland • Small gland attached to 3rd ventricle of brain • Consists of pinealocytes & neuroglia • Melatonin responsible for setting of biological clock • Jet lag & SAD treatment is bright light • light strikes retina and stimulates • suprachiasmatic region of • hypothalamus • stimulates sympathetic ganglion • which then stimulates the • pineal gland • light -> NE -> no melatonin • dark -> lack of NE -> melatonin

42. Thymus Gland • Important role in maturation of T cells • Hormones produced by gland promote the proliferation & maturation of T cells • thymosin • thymic humoral factor • thymic factor • thymopoietin

43. Eicosanoids • Local hormones released by all body cells normally and upon trauma • synthesized from arachidonic acid (fatty acid) • Leukotrienes influence WBCs – inflammation & allergic response • Prostaglandins alter • smooth muscle contraction, glandular secretion, blood flow, platelet function, nerve transmission, metabolism etc. • Ibuprofen & other nonsteroidal anti-inflammatory drugs treat pain, fever & inflammation by inhibiting prostaglandin synthesis • PGs are synthesized by an enzyme complex containing the enzymes COX1 and COX2 • Aspirin and ibuprofen can inhibit activity of COX1 isoform – short term anti-inflammatory • Vioxx, Bextra and Celebrex inhibit activity of COX2 isoform – long term anti-inflammatory

44. Pituitary Gland Disorders • Hyposecretion during childhood = pituitary dwarfism (proportional, childlike body) • Hypersecretion during childhood = giantism • very tall, normal proportions • Hypersecretion as adult = acromegaly • growth of hands, feet, facial features & thickening of skin Thyroid Gland Disorders • Hyposecretion of TSH during infancy results in dwarfism & retardation called cretinism • Hypothyroidism - undersecretion of T3 and T4 • Caused by low production of TSH • in adults produces sensitivity to cold, low body temp. weight gain & mental dullness • Hyperthyroidism – oversecretion of T3 and T4 (Grave’s disease) • caused by the inability of the thyroid to respond to TSH levels • weight loss, cardiac complications, increased fluid behind the eyes & goiter = enlarged thyroid

45. Cushing’s Syndrome • Hypersecretion of glucocorticoids • Redistribution of fat, spindly arms & legs due to muscle loss • Wound healing is poor, bruise easily Addison’s disease • Hyposecretion of glucocorticoids • hypoglycemia, muscle weakness, low BP, dehydration due to decreased Na+ in blood • mimics skin darkening effects of MSH • potential cardiac arrest

46. Diabetes Mellitus & Hyperinsulinism • Diabetes mellitus marked by hyperglycemia • excessive urine production (polyuria) • excessive thirst (polydipsia) • excessive eating (polyphagia) • Type I----deficiency of insulin (under 20) • Type II---adult onset • drug stimulates secretion of insulin by beta cells • cells may be less sensitive to hormone