Endocrine Glands

1. Hypothalamus Pineal gland Pituitary gland Thyroid gland Parathyroid glands Adrenal glands Pancreas Ovary (female) Testis (male) Endocrine Glands

2. Chemical Classification of Hormones • Amine hormones are derived from tyrosine or tryptophan • Include NE, Epi, thyroxine, melatonin • Polypeptide/protein hormones are chains of amino acids • Include ADH, GH, insulin, oxytocin, glucagon, ACTH, PTH • Glycoproteins include LH, FSH, TSH • Steroids are lipids derived from cholesterol • Include testosterone, estrogen, progesterone & cortisol

3. Water Solubility • Polar • water soluble. Cannot pass through cell membrane • Polypeptides, glycoproteins, most amines • Nonpolar (lipophilic) • Insoluble in water but soluble in lipid • Can pass through cell membrane • Steroids and thyroid hormone

4. Common Aspects of Neural & Endocrine Regulation • Target cells with receptor proteins that combine with the regulatory molecule • The binding causes a specific sequence of changes in target cell (Signal transduction leads to response) • There exists mechanisms to quickly turn off the action of the regulator • rapid removal or chemical inactivation • There is an OFF switch as well as an ON switch

5. Mechanisms of Hormone Action

6. Lipophilic hormones • Pass through cell membrane • Bind to intracellular receptors • The hormone-receptor complex acts as a “Transcription factor”. It activates a gene to make an mRNA from which an enzyme protein is made. This enzyme will in some way change the metabolism of the target cell.

7. Hormones That Bind to Nuclear Receptor Proteins • Lipid hormones travel in blood attached to carrier proteins • They dissociate from carriers to pass thru plasma membrane of target • Receptors are located in the cytoplasm or nucleus

8. Polar hormones • Water soluble hormones use cell surface receptors because cannot pass through plasma membrane • Actions are mediated by 2nd messengers • Hormone is extracellular signal; 2nd messenger carries signal from receptor to inside of cell • Some second messengers include: • cAMP • Phospholipase C • Tyrosine kinase • Calcium ions

9. Adenylate Cyclase-cAMP • Mediates effects of many polypeptide & glycoprotein hormones • Hormone binds to receptor causing dissociation of a G-protein subunit

10. Hypothalamus

11. Hypothalamus • Hypothalamus produces ADH and Oxytocin that are transported to the posterior pituitary for release. (more on these later) • Controls the pituitary gland via a variety of releasing and inhibiting factors. • TRH thyrotropin releasing hormone • GHRH growth hormone releasing hormone • CRH corticotropin releasing hormone • Prolactin inhibiting hormone • Etc. etc.

12. Pituitary Gland

13. Pituitary Gland • Pituitary gland is located beneath hypothalamus

14. Stores & releases 2 hormones produced in hypothalamus: Antidiuretic hormone (ADH/vasopressin) which promotes H20 conservation by kidneys Oxytocin which stimulates contractions of uterus during parturition & contractions of mammary gland alveoli for milk-ejection reflex Hypothalamus Neurosecretory cells of the hypothalamus Axon Posterior pituitary Anterior pituitary ADH HORMONE Oxytocin Mammary glands, uterine muscles TARGET Kidney tubules Posterior Pituitary

15. Anterior Pituitary • Secretes 6 trophic hormones that maintain size of targets • High blood levels cause target to hypertrophy • Low levels cause atrophy

16. Anterior Pituitary • Growth hormone(GH) promotes growth, protein synthesis, & movement of amino acids into cells • Thyroid stimulating hormone (TSH) stimulates thyroid to produce & secrete T4 & T3 • Adrenocorticotrophic hormone (ACTH) stimulates adrenal cortex to secrete cortisol, aldosterone

17. Anterior Pituitary • Follicle stimulating hormone (FSH) stimulates growth of ovarian follicles & sperm production • Luteinizinghormone (LH) causes ovulation & secretion of testosterone in testes • Prolactin (PRL) stimulates milk production by mammary glands

18. Anterior Pituitary • Other hormones/products of the pituitary gland include: • MSH - influences skin pigmentation in some vertebrates and fat metabolism in mammals • Endorphins - inhibit the sensation of pain

19. Pituitary Regulation • Release of A. Pit. hormones is controlled by • Hypothalamic releasing & inhibitingfactors • Feedback from levels of target gland hormones • Higher brain centers (via the hypothalamus)

20. Anterior Pituitary continued • Releasing & inhibiting hormones from hypothalamus are released from axon endings into capillary bed in median eminence • Carried by hypothalamo-hypophyseal portal system directly to another capillary bed in A. Pit. • Diffuse into A. Pit. & regulate secretion of its hormones

21. Feedback Control of Anterior Pituitary Target glands produce hormones that feedback to regulate the anterior pituitary and the hypothalamus

22. Higher Brain Function & Anterior Pituitary Secretion • Hypothalamus receives input from higher brain centers that can affect Pituitary secretion • E.g. psychological stress affects circadian rhythms, menstrual cycle, & adrenal hormones

23. Adrenal Gland

24. Adrenal Glands • Sit on top of kidneys • outer cortex • inner medulla

25. Adrenal Glands • Adrenal Cortex • Mineralocorticoids • Aldosterone which stimulate kidneys to reabsorb Na+ and secrete K • Glucocorticoids • Cortisol which inhibits glucose utilization & stimulates gluconeogenesis. Inhibits inflammation, Supresses the immune system

26. Adrenal Medulla • Secretes Epinephrine and Norepinephrine • "fight or flight" response • causes: • Increased respiratory rate • Increased HR & cardiac output • General vasoconstriction which increases venous return • Glycogenolysis & lipolysis • Etc, etc, etc

27. Stress

28. Diseases associated with Adrenal hormone levels • Cushing’s disease • Hyperadrenocorticism • widened face with acne and flushing • fatty deposits over back of neck • stretch marks, easy bruising, hair overgrowth • diabetes mellitus • muscle loss and fatigue • depression and psychosis • moon-like face,  • Addison’s disease • Hypoadrenocorticism • Hyperpigmentation, weight loss

29. Thyroid Gland

30. Thyroid Gland • Is located just below the larynx • Secretes T4 & T3 which set BMR & are needed for growth, development • Also secretes Calcitonin which lowers blood calcium levels

31. Diseases of the Thyroid • Hypothyroidism • People with inadequate T4 & T3 levels are hypothyroid • Have low BMR, weight gain, lethargy, cold intolerance • Hyperthyroidism • Autoimmune disease where antibodies act like TSH & stimulate thyroid gland to grow & oversecrete = hyperthyroidism • Characterized by exopthalmos, weight loss, heat intolerance, irritability/anxiety, high BMR, rapid heart rate

32. Graves’ disease • Graves disease is a form of hyperthyroidism that often presents with exopthalmos

33. Parathyroid Glands • Are 4 glands embedded in lateral lobes of thyroid gland • Secrete Parathyroid hormone (PTH) • Elevates blood Ca2+ levels

34. Calcitonin Thyroid gland releases calcitonin. Reduces Ca2+ uptake in kidneys Stimulates Ca2+ deposition in bones Blood Ca2+ level declines to set point STIMULUS: Rising blood Ca2+ level Homeostasis: Blood Ca2+ level (about 10 mg/100 mL) STIMULUS: Falling blood Ca2+ level Blood Ca2+ level rises to set point Stimulates Ca2+ release from bones Parathyroid gland PTH Increases Ca2+ uptake in intestines Stimulates Ca2+ uptake in kidneys Active vitamin D Parathyroid Hormone and Calcitonin:Control of Blood Calcium • Two antagonistic hormones, parathyroid hormone (PTH) and calcitonin play the major role in calcium (Ca2+) homeostasis in mammals

35. PancreasIslets of Langerhans

36. Islets of Langerhans • Are scattered clusters of endocrine cells in pancreas • Contain alpha & beta cells

37. Islets of Langerhans continued • Betas secrete insulin in response to low blood glucose • Promotes entry of glucose into cells • & conversion of glucose into glycogen & fat • Decreases blood glucose

38. Diabetes Mellitus • Diabetes mellitus is the best-known endocrine disorder • Is caused by a deficiency of insulin or a decreased response to insulin in target tissues • Is marked by elevated blood glucose levels • Type I diabetes mellitus (insulin-dependent diabetes) • Is an autoimmune disorder in which the immune system destroys the beta cells of the pancreas • Type II diabetes mellitus (non-insulin-dependent diabetes) • Is characterized either by a deficiency of insulin or, more commonly, by reduced responsiveness of target cells due to some change in insulin receptors

39. Islets of Langerhans continued • Alphas secrete glucagon in response to low blood glucose during periods of fasting • Stimulates glycogenolysis & lipolysis • Increases blood glucose

40. Pineal Gland • Is located in basal forebrain near thalamus • Secretes melatonin in response to activity of suprachiasmatic nucleus (SCN) of hypothalamus

41. Pineal Gland • SCN is primary timing center for circadian rhythms • Reset by daily light/dark changes • Melatonin is involved in aligning physiology with sleep/wake cycle & seasons • Secreted at night & is inhibited by light • Inhibits GnRH (antigonadotropic) in many animals

42. Gonads: Sex & Reproductive Hormones • Gonads (testes & ovaries) secrete steroid hormones • The testes primarily synthesize androgens, the main one being testosterone • Which stimulate the development and maintenance of the male reproductive system • Estrogens, the most important of which is estradiol • Are responsible for the maintenance of the female reproductive system and the development of female secondary sex characteristics • Progestins, which include progesterone • Are primarily involved in preparing and maintaining the uterus in mammals

43. Testosterone • Testosterone causes an increase in muscle and bone mass and is often taken as a supplement to cause muscle growth

44. Placenta • Placenta secretes estrogen, progesterone, hCG, and numerous polypeptide hormones

45. Autocrine & Paracrine Regulation

46. Autocrine & Paracrine Regulation • Autocrine regulators are produced & act within same tissue of an organ • Paracrine regulators are produced within one tissue & act on different tissue in same organ. • Examples of autocrines & paracrines include: • Cytokines (lymphokines, interleukins) • Growth factors (promote growth & cell division) • Prostaglandins (produced by most organs and have a wide variety of functions)

47. Prostaglandins (PGs) continued • Have wide variety of functions • Different PGs may exert antagonistic effects in tissues • Some promote smooth muscle contraction & some relaxation • Some promote clotting; some inhibit • Promotes inflammatory process of immune system • Plays role in ovulation • Inhibits gastric secretion in digestive system

48. Prostaglandins (PGs) continued • Cyclooxygenase (COX) 1 & 2 are involved in PG synthesis • Are targets of a number of inhibitory non-steroidal anti-inflammatory drugs (NSAIDs) • Aspirin, indomethacin, ibuprofen inhibit both COX 1 & 2 thereby producing side effects • Celebrex & Vioxx only inhibit COX 2 & thus have few side effects

49. Invertebrates • Invertebrate regulatory systems also involve endocrine and nervous system interactions • Example: Control of Metamorphosis in Insects • Brain hormone • Stimulates the release of ecdysone from the prothoracic glands • Ecdysone • Promotes molting and the development of adult characteristics • Juvenile hormone • Promotes the retention of larval characteristics

50. Brain Neurosecretory cells in the brain produce brain hormone (BH), which is stored in the corpora cardiaca (singular, corpus cardiacum) until release. 1 Neurosecretory cells Brainhormone (BH) Corpus cardiacum Corpus allatum LowJH Prothoracicgland Juvenile hormone (JH), secreted by the corpora allata, determines the result of the molt. At relatively high concen- trations of JH, ecdysone-stimulated molting produces another larval stage. JH suppresses metamorphosis. But when levels of JH fall below a certain concentration, a pupa forms at the next ecdysone-induced molt. The adult insect emerges from the pupa. 4 Ecdysone Juvenilehormone(JH) BH signals its main target organ, the prothoracic gland, to produce the hormone ecdysone. 2 EARLYLARVA LATERLARVA PUPA ADULT Ecdysone secretion from the prothoracic gland is episodic, with each release stimulating a molt. 3 Control of molting and development in insects