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Pituitary Gland ( Hypophysis )

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Pituitary Gland ( Hypophysis )

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  1. Pituitary Gland (Hypophysis)

  2. Anterior pituitary hormones are classified into three families: Somatomammotropin family (GH and PRL).Glycoprotein hormones (LH, FSH, and TSH).Opiomelanocortin family (ACTH, β-endorphin, and related peptides).

  3. Growth Hormone(GH)

  4. Human GH consists of 191 amino acid residues (M.W. 22,000) and contains two disulfide bridges. GH = half-life of about 25 minutes in lean adults.GH is inactivated mainly by the liver but also by the kidney. About 40% of the hormone is bound to "GH-binding protein" (GHBP).

  5. The GH and PRL receptors are single-membrane-bound proteins. Each of the receptor contains an extracellular, transmembrane, and intra-cellular domain.GH promotes transport and incorporation of amino acids in skeletal muscle, cardiac muscle, adipose tissue, and liver and is responsible for the proportionate growth of visceral organs and lean body mass during puberty.

  6. GH acts directly on cartilage tissue to promote the endochondral growth that results in skeletal growth; however although GH has a direct effect on chondrocyte stem cells, the growth-promoting effect of GH is due to its stimulation of the chondrocytes to produce insulin-like growth factor I which then acts locally to stimulate cellular replication in the distal proliferative zone of the epiphyseal plate.

  7. GH exerts a "protein-sparing" effect by mobilizing the body's energy substrates, such as glucose, free fatty acids, and ketone bodies, in the same tissues in which it stimulates protein synthesis.GH inhibits glucose uptake by skeletal muscle by inhibiting hexokinase activity and by desensitizing the tissue to the actions of insulin; the effect is to elevate the blood glucose level. GH promotes lipolysisin adipocytes, possibly by increasing the synthesis of hormone-sensitive lipase (HSL), and ketogenesis in the liver.

  8. GH increases the activity of hepatic glucose-6-phosphatase, increasing glucose secretion.These protein-sparing effects of GH are diabetogenicand explain how GH functions as an insulin antagonist.

  9. GH hypersecretion in children causes increased growth rate and can result in gigantism. GH excess occurs infrequently in childhood, and most frequently in middle-aged adulthood, which leads to acromegaly (acral -- extremities + megas -- large), a condition in which the cartilaginous tissues proliferate, resulting in distorted overgrowth of the hands, feet, mandibles, nose, brow, and cheek bones.

  10. The major cause of GH resistance is a genetic defect in the growth hormone receptor (GHR) and the resultant condition is known as Laron-type dwarfism

  11. Prolactin

  12. Human prolactin (PRL) contains 199 amino acid residues (M.W. 23,500) and three intramolecular disulfide bridges.In healthy adults the anterior pituitary releases very little PRL under nonstressed conditions, primarily because PRL release is under hypothalamic inhibition.This inhibition is exerted by dopamine or PIH.

  13. Elevated levels of PRL stimulate milk production in the mammary gland. After parturition, PRL promotes milk secretion via a neuroendocrine reflex that involves sensory receptors in the nipples. In mammary tissue, prolactin binds to alveolar cells and stimulates the synthesis of milk-specific proteins (casein, lactalbumin, and lactoglobulin) by increasing production of their respective mRNAs.

  14. The Opiomelanocortin Family • ACTH

  15. ACTH

  16. ACTH is a polypeptide of 39residues.The first 24 of which are required for corticotropic activity and do not vary among species. Because (ACTH) contains the MSH sequence in residues 6-9 (His-Phe-Arg-Trp), ACTH has intrinsic melanocyte-stimulating activity.ACTH can thus cause skin darkening if present in high concentrations.

  17. ACTH acts mainly on the cells of the zona fasciculate of the adrenal cortex to stimulate the synthesis and release of cortisol. It also stimulates the secretion of adrenal androgens from the zonareticularis. Binding of ACTH to receptors activates formation of cAMP which mediates cortisol formation and secretion and protein synthesis.

  18. β-Endorphin

  19. β-Endorphin is a 31-amino-acid polypeptide released together with ACTH. When introduced into the third ventricle of the brain, it produces dramatic behavioral changes, but when injected systemically, it does not. Thus, the function of circulating β-endorphin remains unclear.

  20. β-Endorphinis an agonist of the opioid receptors, with evidence suggesting it serves as the endogenous ligand of the μ-opioid receptor, the same receptor to which the chemicals extracted from opium, such as morphine, have their analgesic and addictive effects (indeed, the μ-opioid receptor was named based on its most renowned ligand, morphine).

  21. Melanocyte-stimulating hormone(MSH)

  22. The melanocyte-stimulating hormones (collectively referred to as MSH or intermedins) are a class of peptide hormones that are produced by cells in the intermediate lobe of the pituitary gland.

  23. They stimulate the production and release of melanin (melanogenesis) bymelanocytes in skin and hair. MSH signals to the brain have effects on appetite and sexual arousal.

  24. Melanocyte-stimulating hormone belongs to a group called the melanocortins. This group includes ACTH, alpha-melanocyte-stimulating hormone (α-MSH), beta-melanocyte-stimulating hormone (β-MSH) and gamma-melanocyte-stimulating hormone (γ-MSH); these peptides are all cleavage products of a large precursor peptide called pro-opiomelanocortin (POMC). α-MSH is the most important melanocortin for pigmentation.

  25. Glycoprotein Hormones • 1.Thyroid-stimulating hormone (TSH, thyrotropin) • 2. Luteinizing hormone (LH) and follicle stimulating hormone (FSH)

  26. 1. Thyroid-stimulating hormone (TSH, thyrotropin)

  27. TSH stimulates secretion of the thyroid hormones T4 and T3. TSH stimulates synthesis of thyroid hormone, synthesis of thyroglobulin, synthesis of RNA and protein, uptake and utilization of glucose, and synthesis of phospholipids.

  28. TSH action is mediated by intracellular cAMP Release of TSH is stimulated by TRH and inhibited by circulating T4.T4 is converted to T3 by 5'-deiodinase.In the normal adult, the pituitary contains about 0.3 mg TSH, and the basal level of the hormone in blood is about 1 ng/mL.

  29. 2. Luteinizing hormone (LH) and follicle stimulating hormone (FSH)

  30. LH and FSH are synthesized within the same gonadotrophs but are products of different genes. They differ in carbohydrate composition (and thus in clearance rates); although their β subunits have the same number of amino acid residues, they differ in amino acid sequences.

  31. Adrenal Glands

  32. The adrenal glands, a pair of well-vascularized glands positioned bilaterally above the cranial poles of the kidney, consist of two embryologically, histologically, and functionally distinct regions.

  33. The outer region of each (adrenal cortex) accounts for about 80% of the weight of the gland and produces steroid hormones.The inner core of each gland (adrenal medulla) that has assumed an endocrine function, and synthesizes and secretes catecholamines and enkephalins.

  34. Aldosterone

  35. The major regulators of aldosterone secretion are the renin-angiotensin system and extracellular potassium ions (K+). The renin-angiotensin system is sensitive to changes in intravascular volume and arterial pressure. While potassium ions is an aldosterone-regulated substance that feeds back to reduce aldosterone synthesis (simple negative feedback).