1. Dr. Eman El Eter The pituitary Gland: Anterior pituitary hormones. Posterior pituitary hormones

2. Hypothalamic Hypophyseal Control

3. Anterior pituitary hormones

4. Pituitary glands Anterior pituitary hormones ◦ GH ◦ Prolactin Posterior pituitary hormones ◦ ADH ◦ Oxytocine

5. Growth hormone (Somatotropin)

6. Growth Hormone (Somatotropin) Structure and Source of Growth Hormone: GH is a large peptide hormone, with 191 amino acids GH is produced by somatotroph cells of the anterior pituitary

7. Transport of GH in the Blood About 50% of GH is found in the blood bound to a Growth Hormone-Binding Protein (GHBP). GHBP increases the half-life of GH, but decreases biological activity (bound GH is not biologically available). The GHBP is identical to the ligand binding domain of the GH receptor, and may be derived from alternative splicing of the GH receptor RNA.

8. Growth Hormone (GH; Somatotropin ) The major hormone regulating growth in the body. Actions of Growth Hormone: - increases skeletal growth - increases muscular growth - increases amino acid uptake and protein synthesis by the cells. - increased use of lipids for energy - decrease glucose re-uptake by the cells & increases blood sugar level. - decreased storage of carbohydrates

9. Growth Growth Hormone actions

10. Role of Somatomedins in GH Actions – the GH/IGF Axis The effects of GH on skeletal and muscular growth appear to be due to the activity of somatomedins, or insulin-like growth factors (IGF- 1 and IGF-2) – processed in the liver. GH acts on the liver, and some other tissues, to increase the production of IGFs. IGFs then enter the circulation and act on target tissues to enhance growth. They increase protein synthesis in skeletal muscles.

11. Regulation of GH Expression in Somatotrophs GHRH AC Gs cAMP PKA PIT-1 GH synthesis Gi (-) somatostatin A txn factor in the Pit

12. Control of GH secretion: 1. The hypothalamus: a. GHRH   GH secretion. b. GHIH (somatostatin)   GH secretion 2. Hypoglycemia (fasting)   GH secretion. (N.B. glucose intake   GH secretion). 3. Muscular exercise   GH secretion. 4. Intake of protein or amino acids   GH secretion (after meals).

13. Control of GH secretion: 5. During sleep   more in children. 6. Stress conditions, e.g. trauma or emotions   GH secretion. 7. FFAs   GH secretion

14. Regulation of GH Levels GH is released from the pituitary in a pulsatile manner: hormone level time GH levels are low during the day, but increase during sleep. There is an overall increase in GH levels during puberty.

15. Abnormalities of GH secretion  GH secretion:  Signs & symptoms ‘ in childhood ’ : Gigantism,  all body tissues grow rapidly, including bones. Height  as it occurs before epiphyseal fusion of long bones w their shafts. Hyperglycemia (diabetes).

16. Abnormalities of GH secretion  GH secretion:  Signs & symptoms ‘in adults’: Acromegally, person can’t grow taller, soft tissue continue to grow in thickness (skin, tongue, liver, kidney, …)= organomegally - Enlargement of bones of hands & feet. - Enlargement of membranous bones including cranium, nose, forehead bones, supraorbital ridges. - Protrusion of lower jaw (Proganthism). - Hunched back (kyphosis) (enlargement of vertebrae).

17.  GH = pituitary dwarfism Manifestations: -Short stature. -Proportionate growth -No mental retardation.

18. 18 Hypopituitarism It is hypofunction of the pituitary gland. It results from disease of the pituitary gland itself (destruction of the anterior lobe) or of the hypothalamus. Panhypopituitarism is total absence of all pituitary secretions and is rare. Postpartum pituitary necrosis is more likely to occur in women with severe blood loss, hypovolemia, and hypotension at the time of delivery. It can be a complication of radiation therapy. The total destruction of the pituitary gland results in extreme weight loss, emaciation, atrophy of all endocrine glands and organs, hair loss, impotence, amenorrhea, hypometabolism, and hypoglycemia. Coma and death may occur.

19. Panhypopituitarism/Hypopituitarism Manifestations are due to deficiency of hormones secreted by pituitary gland: Gonadotropin deficiency: ◦ Women: Amenorrhea, Infertility ◦ Men: Decreased libido, Decreased beard and body hair. Corticotropin deficiency: ◦ Fatigue, Decreased appetite, Weight loss, Decreased pigmentation, Abnormal response to stress, Hypotension, Hyponatremia, Fever. Thyroxin deficiency: ◦ Fatigue, Cold intolerance. Deficiency of ADH: ◦ Polyuria & Polydipsia

20. Prolactin Prolactin (PRL), known as luteotropin. A Protein hormone that in humans is best known for its milk production effect. Prolactin is secreted from the pituitary gland in response to mating, estrogen treatment, ovulation, and nursing. Prolactin is secreted in a pulsatile fashion in between these events. Prolactin also plays an essential role in metabolism, regulation of the and immune system.

21. Functions of prolactin ◦ The major function of prolactin is milk production (synthesis) release is inhibited by PIH (dopamine) secreted by the hypothalamus. suckling response inhibits PIH release and stimulates prolactin secretion.

22. Target cells Prolactin Oxytocin

23. Hyperprolactenemia Manifestation: Galactorrehea : Milk secretion in non-lactating female. Infertility (in males& females): as it competes with FSH at receptor site : ovaries/testis. Gynecomastia (males) Cause: Prolactenoma Treatment: Medical: bromocreptin Surgical.

24. The posterior pituitary gland  Composed mainly of cells called ‘Pituicytes’, which act as packing & supporting cells.  Stores & releases hormones into the close capillaries.  These hormones are produced in hypothalamus.

26. Secretion of Posterior Pituitary Hormones

27. The posterior pituitary gland hormones  Posterior pituitary gland releases 2 hormones: 1. Antidiuretic hormone (ADH), or arginine vasopressin (AVP). 2. Oxytocin  Both hormones are produced in hypothalamic nuclei: - Supraoptic nucleus  (ADH + 1/6 oxytocin) - Paraventricular nucleus  (Oxytocin + 1/6 ADH)

28. The posterior pituitary gland hormones … cont.  Both hormones are polypeptides, each contains 9 amino acids. Both are transported slowly along the ‘ hypothalamo-hypophyseal tract ’ in combination with carrier protein called ‘ neurophysin ’, to the nerve endings in the posterior pituitary gland where they are stored.

29. Actions of ADH  ADH has 2 m ain effects: 1.  water re-absorption (retention) by distal tubules & collecting ducts of the kidneys  decrease osmotic pressure of the blood. * This effect is regulated by V2 V2 receptors, through the action of cAMP. 2. Contraction of vascular smooth muscles  generalized vasoconstriction. * This effect is regulated by V1 V1 receptors, through the action of IP 3 /Ca 2+.

30. Actions of ADH (vasopressin)

31. Control of ADH release 1.  in osmotic pressure of the ECF ( ( in plasma osmolality), as in dehydration which will stimulate osmoreceptors in the hypothalamus   ADH. Hyperosmolarity of ECF Receptors in hypothalamus More ADH releaseThirst Collecting ducts of kidneys Reabsorption of water  Water intake Dilution of ECF -ve feedback

32. Control of ADH release …cont. 3.  arterial blood pressure, due to  blood volume   ADH. 4. Age:   ADH secretion  water retention & hyponatremia. 5. Pain, emotional stress & physical trauma   ADH secretion. 6. Drugs, e.g. morphine, barbiturates, & nicotine   ADH secretion. 7. Alcohol   ADH secretion.

33. Inputs reflexly controlling thirst.

34. Control of ADH Release Osmotic stimuli: ◦ Osmoreceptor mediated ◦  osmolality   ADH secretion ◦  osmolality   ADH secretion Non-osmotic stimuli (Volume effects) ◦ Baroreceptor mediated (vagus nerve) ◦  blood pressure   ADH secretion ◦  blood pressure   ADH secretion

35. Oxytocin

36. Functions of oxytocin Breast-feeding ◦ contracts the myoepithelial cells of the alveoli (classic neuroendocrine reflex): milk let down reflex. Childbirth (parturition) ◦ in late pregnancy, uterine smooth muscle (myometrium) becomes sensitive to oxytocin due to the synergistic effect of estrogen. During labor stretch of cervix enhances oxytocin release in a positive feedback manner.

37. Milk Letdown reflex

38. Example of positive feedback mechanism

40. Summary of posterior pituitary hormones actions