Endocrine System

1. Endocrine System • Overview • Hypothalamus and pituitary gland • Hormones, receptors and their actions • Second messengers

2. Cell-Cell Communication • Necessary for integration of body activities • Mechanisms • neurotransmitters • released from neurons to travel across gap to 2nd cell • gap junctions • holes in cell membranes between cells: links cells electrically and metabolically • paracrine (local) hormones • secreted into tissue fluids to affect nearby cells

3. Endocrine cell Endocrine tissue Hormone Blood Interstitial space Target tissue Components of Endocrine System • Endocrine glands • produce hormones • Hormone • chemical messenger secreted into bloodstream, stimulates response in another tissue or organ • Target cells • have receptorsfor hormone

4. Differences in Nervous and Endocrine Systems • Means of communication • nervous system has both electrical and chemical methods • endocrine system has only chemical methods • Speed and persistence of response • nervous system reacts quickly (1 - 10 msec) and stops quickly • endocrine system reacts slowly (hormone release in seconds or days), effect may continue for weeks • Area of effect • nervous system effects are targeted and specific (one organ or tissue) • endocrine system may have general, widespread effects on many organs

5. Similarities in Nervous and Endocrine Systems • Several chemicals function as both hormones and neurotransmitters • norepinephrine, epinephrine, dopamine • Some hormones secreted by “neuroendocrine” cells (neurons) • oxytocin and antidiuretic hormone • Overlapping effects on same target cells • norepinephrine and glucagon cause glycogen hydrolysis in liver • Systems regulate each other • neurons trigger hormone secretion • hormones stimulate or inhibit neurons

6. Endocrine Organs

7. Hypothalamus Regulates primitive functions from water balance to sex drive Many functions carried out by pituitary gland Pituitary Gland (Hypophysis) Suspended from hypothalamus by stalk (infundibulum) Posterior and anterior parts Hypothalamohypophyseal Axis

8. Hypothalamohypophyseal tract

9. Hypothalamohypophyseal portal system

10. Hypothalamohypophyseal Portal System • Hormones (red box) secreted by anterior pituitary (under control of hypothalamic releasers and inhibitors) Gonadotropin- releasing hormone controls FSH + LH release Thyrotropin- releasing hormone Corticotropin- releasing hormone Prolactin- releasing hormone Prolactin- inhibiting hormone GH- releasing hormone Somatostatin • Hormones secreted by hypothalamus, travel in portal system to anterior pituitary

11. Pituitary Hormones - Anterior Lobe • Tropic hormones target other endocrine glands • gonadotropins target gonads, FSH (follicle stimulating hormone) and LH (luteinizing hormone) • TSH (thyroid stimulating hormone) • ACTH (adrenocorticotropic hormone) • PRL (prolactin) • GH (growth hormone )

12. Pituitary Hormone ActionsAnterior Lobe Hormones • FSH • ovaries, stimulates development of eggs and follicles • testes, stimulates production of sperm • LH • females, stimulates ovulation and corpus luteum to secrete progesterone and estrogen • males, stimulates interstitial cells of testes to secrete testosterone • TSH • stimulates growth of gland and secretion of thyroid hormone (TH) • ACTH or corticotropin • regulates response to stress, stimulates adrenal cortex to secrete of corticosteroids that regulate glucose, fat & protein metabolism • PRL • female, milk synthesis after delivery • male,  LH sensitivity, thus  testosterone secretion • GH or somatotropin • promotes tissue growth

13. Pituitary Hormones - Posterior Lobe • Stores and releases oxytocin and ADH • ADH • targets kidneys to  water retention, reduce urine • Oxytocin • labor contractions, lactation • possible role sperm transport, emotional bonding

14. Hormone Chemistry • Steroids • derived from cholesterol • lipid soluble; water insoluble; hydrophobic • act via intracellular receptors • turn on gene transcription • sex steroids, corticosteroids

15. Hormone Chemistry • Steroids • Polypeptides and proteins • small proteins made by ER/GN • often processed and modified • water soluble; hydrophilic • act via membrane-bound receptors • modify existing metabolic proteins • Oxy, ADH; all releasing and inhibiting hormones of hypothalamus; most of anterior pituitary hormones

16. Hormone Chemistry • Steroids • Polypeptides and proteins • Monoamines (biogenic amines) • derived from amino acids (usually tyrosine) • water soluble; hydrophilic • act via membrane-bound receptors • modify existing metabolic proteins • catecholamines (norepinephrine, epinephrine, dopamine) and thyroid hormones

17. Hormone Transport • Monoamines and peptides/proteins are hydrophilic so mix easily with blood plasma – dissolved • Steroids and thyroid hormone are hydrophobic and must bind to transport proteins for transport • bound hormone - hormone attached to transport protein, (prolongs half-life to weeks, protects from enzymes and kidney filtration) • only unbound hormone can leave capillary to reach target cell (half-life a few minutes) • Transport proteins in blood plasma

18. Hormone Receptors • Located on plasma membrane (membrane-bound) or intracellular (soluble within cytoplasm or nucleus) • sometimes found on the membrane of mitochondria and other organelles, • usually thousands for given hormone • turn activities on or off when hormone binds • metabolic pathways • gene expression • Exhibit specificity and saturation

19. Hormone Mode of Action • Hydrophobic hormones (steroids and thyroid hormone) penetrate by diffusion of the plasma membrane • ultimately enter nucleus • Hydrophilic hormones (monoamines and peptides) can not pass through membrane so bind to membrane-bound receptors • 2nd messenger activation

20. Which is it?

21. Receptor Response to Ligand Change shape, change function activate internal proteins, enzymes, transcription factors etc

22. Membrane Receptor ActionIon Channel Activation • Hormone binding to receptor results in depolarization or hyperpolarization of the membrane

23. Membrane Receptor ActionG-protein Activation • Hormone binding to receptor results in modification (activation or inhibition) of “downstream” enzymes and 2nd messenger formation or degradation

24. L L L E E* R* E R* a a* R g a g g g g g GDP GTP b b b b b b GTP GDP GDP L E* R* a* GTP GDP

25. Second Messengers • Cyclic nucleotides (cAMP, cGMP) • Diacylglycerol (DAG) • Inositol triphosphate (IP3) • Calcium

26. cAMP as a Second Messenger 1) Hormone binding activates G protein 2) GP activates adenylate cyclase 3) AC produces cAMP 4) cAMP activates kinases 5) Kinases activate enzymes 6) Metabolic reactions: synthesis, secretion, degradation, altered membrane potentials

27. Membrane Receptor ActionEnzyme Receptor Activation • Hormone binding to receptor results in activation of intrinsic (receptor) enzyme and “downstream” metabolic changes

28. Membrane Receptor ActionIntracellular Receptors • Hormone binding to receptor results in activation of transcription factors and gene expression

29. Hormone Hormone Membrane -bound Intracellular receptor receptor Receptor linked Receptor linked Receptor linked Activates to ion channel to G protein to enzyme genes Opens or closes Activates already Synthesizes Ion channels existing enzymes enzymes Cell Response Summary of Hormonal Actions

30. Regulation of Hormone Secretion • Non-hormonal • Control of release dependent upon concentration of other non-hormonal substance (i.e., glucose)

31. Regulation of Hormone Secretion • Non-hormonal • Neuronal • Secretion or inhibition of release influenced by emotions or stress

32. Regulation of Hormone Secretion • Non-hormonal • Neuronal • Hormonal • Control of release regulated by other hormones

33. Review questions • What are the different methods of cell to cell signaling? Provide an example of where/when each method occurs. • Name and approximately locate the main endocrine glands. • Compare and contrast the nervous and endocrine systems. • Describe the relationship between the hypothalamus and the pituitary gland. What is the tract system? What about the portal system? • Which hormones are released from the anterior pituitary and which from the posterior pituitary? Briefly describe the actions of these hormones on their targets. • What are releasing and inhibiting hormones? Where are they released from? What is there target (usually)? • Compare and contrast the main classes/types of hormones and their receptors. • What different ways do membrane-bound receptors act upon their target cell? Provide an example of each of these types of activity. • Explain how intracellular receptors differ from membrane-bound receptors (include cellular location and mechanism of action). • Briefly summarize the cellular effect of hydrophilic hormone activation and hydrophobic hormone activation. • What are second messengers and why are they important? Be able to provide at least one example of cAMP acting as a second messenger. • How is hormonal release regulated? Provide an example for each way.