Chemical Classification of Hormones (continued)

2. Chemical Classification of Hormones (continued) • Glycoproteins: • Long polypeptides (>100) bound to 1 or more carbohydrate (CHO) groups. • __________________.

3. Hormone receptors Cells of target organ have specific receptors for hormones. Hormone binds to receptor and stimulates a specific cellular response - protein & peptide hormones - receptor is in ____________________ - steroid hormones - receptor is in ________ - prostaglandin hormones - receptor is in _______________________ 1.___________of receptors on or in cell regulate degree of cell stimulation and cellular response to the hormone 2. ______________ can regulate whether there is a increase or decrease in the number of receptors Lack of _____________ receptor in male - Testicular Feminization

4. Hormone Transport • Transport mechanism depends on hormone ____________ • Protein hormones – __________ – carried in dissolved form • Steroid & Thyroid hormones – _____________– have limited solubility in aqueous solution (plasma) • These hormones – ______– specific and nonspecific carriers • Hormones must penetrate cell or bind to specific receptors ____________) to initiate action • Are only about 1% of hormones are unbound

5. What is a 2nd messenger??? • Some hormones __________ enter the cell • Bind to receptors on cell membrane • Hormone = messenger • _______________ = relays info from the hormone to the inside of the cell

6. Hormones That Use 2nd Messengers • Hormones that cannot pass through plasma membrane use 2nd messengers. • ____________, __________, and glycoprotein hormones bind to receptor proteins on the target plasma membrane. • Actions are mediated by 2nd messengers (signal-transduction mechanisms). • Extracellular hormones are transduced into intracellular 2nd messengers.

7. Hormones That Bind to Nuclear Receptor Proteins • Lipophilic steroid and thyroid hormones are attached to __________ carrier proteins. • dissociate from ___________ and diffuse across membrane • Receptors on nucleus for the lipophilic hormones are known as nuclear ______________. • Complex binds with _____ • Activates genes – mRNA –Ribosome – new or more protein (enzymes etc)

8. Steroid Hormones Steroid Hormones Receptors are mainly in the nucleus Glucocorticoids receptors are mainly in the cytoplasm Capillary Steroid Release from blood circulation Progesterone Uterine Glandular Epithelial Cell Diffuses in cytoplasm DNA Rough Endoplasmic Reticulum Steroid Nucleus Chromatin Secretion Protein Synthesis mRNA Receptor Bilaminar Cell Membrane

9. What is a 2nd messenger??? • 1. Adenylate –Cyclase- cyclic AMP • 2. Phospholipase C-Ca • 3. Tyrosine kinase

10. Adenylate Cyclase-cAMP: Table 11.4 • Polypeptide or glycoprotein hormone binds to receptor protein causing dissociation of a subunit of _______________. • G-protein subunit binds to and activates adenylate cyclase. • ATP cAMP + PPi • cAMP attaches to inhibitory subunit of protein kinase. • Inhibitory subunit dissociates and activates protein kinase.

11. Adenylate Cyclase-cAMP (continued) • ______________ enzymes within the cell to produce hormone’s effects. • Modulates activity of enzymes present in the cell. • Alters metabolism of the cell. • cAMP inactivated by phosphodiesterase. • Hydrolyzes cAMP to inactive fragments.

12. Ca2+ 2nd messenger system 2 1 3 6 4 Ca + Calmodulin See Table 11.5 7 = Calmodulin activates protein kinase 8 = response to hormone

13. Epi Can Act Through Two 2nd Messenger Systems

14. Tyrosine Kinase • Insulin receptor consists of 2 units that _________ when they bind with insulin. • Insulin binds to ligand–binding site on plasma membrane, activating enzymatic site in the cytoplasm. • Autophosphorylation occurs, increasing tyrosine kinase activity. • Activates signaling molecules. • Stimulate_______, _______ and ___________ synthesis.

15. Tyrosine Kinase (continued)

16. Hypothalamus & Pituitary Glands • Hypothalamus – control center • Numerous autonomic nervous system control functions • Hypothalamic – releasing hormones • – travel to anterior pituitary • Causes release of other hormones • http://www.ansi.okstate.edu/resource-room/reprod/all/animations/ see HP Clip

17. Pituitary Gland • Hypophysis or hypophysial gland • Location___________ sella turcia (bone pocket) • Structurally and functionally divided into: • Neurohypophysis – pars nervosa or posterior lobe • Adenohypohyysis – pars distalis – anterior lobe • Communicates with hypothalamus

18. Pituitary Gland (continued) • Posterior pituitary (neurohypophysis): • Formed by down growth of the ______ during fetal development. • Composed of axons with neural origin – primarily from supraoptic and paraventricular nuclei of hypothalamus • Mainly an extension of hypothalamus • ______________ in hypothalamus • Axons form stalk to the posterior pit • Nerve endings in the actual lobe • Nerve cell bodies in hypothalamus = hormone source. • Hormones carried down axoplasm into post pit – stored until release

19. Posterior pituitary: Stores and releases 2 hormones that areproduced in the hypothalamus: ADH & Oxytocin Antidiuretic hormone (ADH/vasopressin): Promotes the retention of H20 by the kidneys. Alcohol inhibits release of ADH = increased urination Works to maintain blood pressure by regulation of water in blood Increases blood pressure – via contraction of SM Stimulates glycogenolysis Increases water readsorption – kidney nephrons Diabetes insipidus – lack of ____________ = dilute urine + excess amounts of urine (polyuria) and large amount of fluid intake (polydispsia) Diabetes Mellitus – lack of ____________________ Also large amounts of urine – but urine contains large amounts of glucose Pituitary Hormones (continued)

20. Pituitary Hormones (continued) • Posterior pituitary: • Antidiuretic hormone (ADH/vasopressin): • Receptors for ADH response: • _____________ – in hypothalamus, esophagus, and stomach • _____________receptors – sense blood volume in atria of heart • _______________ – carotid sinus and aortic arch • Sense pressure

21. Pituitary Hormones (continued) • Posterior pituitary: Antidiuretic hormone (ADH/vasopressin): • Stimuli for ___________ release: • Osmotic pressure • Decrease in blood volume (hemorrhage) • Morphine, nicotine, barbituates • Pain, emotion, stress, exercise • Stimuli that inhibit ADH release: • _________________ (both ADH & Oxytocin) • _________________

22. Pituitary Hormones (continued) Oxytocin: • Functions: promote ____________ • Stimulates contractions of the uterus (myometrium) during parturition. • Stimulates contractions of the mammary gland alveoli (myoepithelial cells) . • _______________________ reflex. • Prior to parturition – ________________ of oxytocin receptors via other hormones • If not, would be running around lactating and having uterine contractions all the time.

23. Posterior Pituitary: Oxytocin Hypothalamus Neural Pathway to Hypothalamus Neuroendocrine Cells Synthesis Oxytocin Nerve Cells Spinal Cord • Oxytocin • stored in nerve terminal stimulation of nerve releases oxytocin in capillary • contraction of myoepithelial cells for milk letdown • - causes milk from Aveoli to release into glands • Also causes: • - Stimulation of cervix at parturition • - Clitoral and ejaculation response Posterior Pituitary (Neurohypophysis) Capillaries Oxytocin Release in Blood Calf Stimulation of Mammary Gland

24. Pituitary Gland (continued) Anterior pituitary: • Master gland (adenohypophysis). • Derived from a pouch of epithelial tissue that migrates upward from the mouth. • Consists of 2 parts: • Pars distalis: ________________. • Pars tuberalis: thin extension in contact with the infundibulum. • No neural connection between hypothalamus and ant pit. • Under control of hypothalamic releasing hormones • Primarily produce peptides (AA) except for _______________(catecholamine)

25. Pituitary Gland (continued) Anterior pituitary: • Releasing hormones – synthesized by hypothalamic neurons • Neurons terminate at the _________________ (around portal vessles) • AP down neurons – release hormones into capillaries – carried via portal blood vessels to ant pit. • Hormones can be stimulatory or inhibitory

26. Pituitary Hormones Anterior Pituitary: • ____________effects: • High blood hormone causes target organ to hypertrophy. • Low blood hormone causes target organ to atrophy. • 6 different hormones released but all have similar affects

27. Pituitary Gland (continued) Anterior Pituitary: • 1. Growth Hormone (Somatotropin) • 1. ____________– stimulates growth of body cells – esp bone and muscle • 2. Anabolism – increases _________ transport into the cells • Insulin like affect because insulin also causes not only glucose uptake but AA as well • _________________: opposite of anabolism – breaks cells down • 3. Increases fat metabolism – lipolysis (anti-insulin) • Increases FFA levels in blood to provide energy • Fasting & stress • When should you “work out”? • 4. Increases blood glucose • 5. _________________ – increases milk production

28. Pituitary Gland (continued) • Anterior Pituitary: GH • 1.Young Animal: Excess GH = _________ • Increase in long bones • Epiphyseal cartilage – • Continue to grow until puberty (how we know if a sheep is a lamb or mutton) • Then no additional linear growth • 2. After puberty = ________ – continual growth in areas which have responsive cartilage • Jawbone, hands, face, feet – thick coarse skin & muscle hypertrophy • Lower GH = ___________– decreased development & no puberty or adult sexual development.

29. Pituitary Gland (continued) • Anterior Pituitary: ____________ • Increases mammogenesis – pregnancy & lactation following birth • Decrease prolactin = no lactation • Fescue toxicosis = cows, horse, sheep • Decrease in prolactin, especially problematic in horses

30. Prolactin • Secreted from anterior pituitary • In Mammals, mammary gland development and milk production • Receptors are everywhere • Induces __________ growth in rabbit, rodent, humans. Maintains in dos, rodents an skunks • Chickens- depresses LH, FSH, causes broodiness • Blocks GnRH, stopping ovulation cycles Dopamine Stimulatory factors (-) (+) Estrogen (+) Prolactin * Target Tissues

31. Pituitary Gland (continued) • Anterior Pituitary: Thyroid Stimulating Hormone • Regulates size & secretory activity of gland • Cold stress = ____________in TSH activity • Decrease TSH activity = __________ • Excess TSH activity = hyperthyroidism

32. Pituitary Gland (continued) • Anterior Pituitary: Adrenocorticotropic hormone (ACTH) • Stimulates outer portion of adrenal glands (__________) • Adrenal cortex has 3 principal classes of hormones • 1. _______________ – cortisol and corticosterone • 2. mineralocorticoids – ______________________ • 3. androgens – sex steroids • Stress and hypoglycemia (low blood sugar) = increase in ACTH

33. Pituitary Gland (continued) • Anterior Pituitary: Leutenizing hormone • Stimulates _________________ – ovary – • corpus luteum – progesterone • Follicle – estrogen • Maturation of____________ • Ovulation • Formation of CL • Both LH & FSA – maturation of graafian follicle • Stimulates __________ secretion in males (interstitial cells of testes)

34. Pituitary Gland (continued) • Anterior Pituitary: Follicle stimulating hormone (FSH) • _________ – trigger, promote development • Stimulates follicle cells – __________ • In males – development seminiferous tubules & maintenance of spermatogenesis • Deficiency = delayed _______ or amenorrhea • Excess = precocious puberty (less than 8 yrs old in humans; less than 10 in males)

35. Hypothalamus-Anterior Pituitary interrelationship • ________________ portal system caries hypothalamic hormones specifically to the anterior pituitary without dilution in the systemic blood. • 1. Allows rapid response • 2. Little dilution of peptide hormones • 3. Peptide hormones have short 1/2 life • Specific hypothalamic nuclei secrete releasing or release • inhibiting factors that control release of pituitary hormones.

36. Hypothalamic Control of Posterior Pituitary • Hypothalamus neuron cell bodies produce: • ADH: supraoptic nuclei. • Oxytocin: paraventricular nuclei. • Transported along the hypothalamo-hypophyseal tract. • Stored in posterior pituitary. • Release controlled by neuroendocrine reflexes.

37. Hypothalamic Control of the Anterior Pituitary • Hormonal control rather than neural. • Hypothalamus neurons synthesize releasing and inhibiting hormones. • Hormones are transported to axon endings of median eminence. • Hormones secreted into the hypothalamo-hypophyseal portal system regulate the secretions of the anterior pituitary

38. Question: • Does the posterior pituitary produce any hormones? • NO!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!

39. Mechanism of Thyroid Hormone Action • Thyroxine (tetraiodothyronine) T4 • Travels attached to ____________ (thyroxine-binding globulin) • Small amount of __________ • Carrier proteins have a ___________affinity for T4 • Free T3 is what is physiologically active • So, why do we have T4??? • T4 passes into cytoplasm and is converted to T3. • Receptor proteins located in nucleus.