ENDOCRINOLOGY

1. ENDOCRINOLOGY Lec. 4 Dr. Ali al-bayati

2. Hypothalamic – Pituitary Axis

3. Neurosecretory neurons Hypothalamus Hypophysiotropic H.: ●● 1 Systemic arterial inflow 2 Anterior pituitary Hypothalamic-hypophyseal portal system 3 6 System venous outflow 4 Posterior pituitary 5 • Anterior pituitary hormones:

4. The hypothalamus is derived from forebrain tissue on either side of the third ventricle and links the nervous system to the endocrine systems through the pituitary gland. The hypothalamus produces two types of endocrine factors; • The hypothalamic neuropeptides • The hypothalamic releasing factors. • The releasing factors are neurosecretions synthesized in the hypothalamus and released through the hypothalamic pituitary portal circulation. They have their effect on the secretion of pituitary tropic hormones.

6. (oxytocin) and ADH • produced in hypothalamus • transported by hypothalamic-hypophyseal tract to posterior lobe (stores/releases hormones) Vasopressin (Antidiuretic Hormone, ADH) • Also known commonly as arginine vasopressin, is a nine amino acid peptide • Within hypothalamic neurons, the hormone is packaged in secretory vesicles with a carrier protein called neurophysin Osmoreceptors in the hypothalamus regulate the amount of ADH released.

7. Functions of ADH; • ADH has two major effects. • peripheral vasoconstriction • ADH regulates water loss via kidney • ADH binds to membrane receptor in kidney’s tubules and activates adenylate cyclase. The cyclic AMP thus produced will activate the protein kinase. water channel proteins

8. Vasopressin is responsible for increasing water absorption in the collecting ducts of the kidney nephron. • The major stimulation of ADH secretion are: Hyperosmolality and decrease ECF volume. • The physiological ADH release occur with plasma osmolality in a narrow range (284-295 mOsm/kg) • Thus when plasma osmolality. • < 280 mOsm/kg ــــــــــــــــــــــ> ADH secretion↓ • When > 290 mOsm/kgــــــــــــــــــ> ADH secretion ↑ • And when ECF volume ↓ـــــــــــــــــ> ADH secretion ↑ • When ECF volume ↑ــــــــــــــــــــــــــ> ADH secretion ↓ • Thirstwill stimulate ADH secretion. • The half – life of ADH is 10-20 min.

9. The major stimulation of ADH secretion are:1- Hyperosmolality2- Decrease in ECF volume.

12. Lowering of the osmolality (hemodilution) suppresses ADH secretion. Conversely, an increase in osmolality (hemoconcentration or dehydration) leads to stimulation of the secretion of ADH. • Deficiency of ADH results in diabetes insipidus. • Hypothalamic ("central") diabetes insipidus results from a deficiency in secretion of antidiuretic hormone from the posterior pituitary. Causes of this disease include head trauma, and infections or tumors involving the hypothalamus & anterior pituitary. • Nephrogenic diabetes insipidus occurs when the kidney is unable to respond to antidiuretic hormone. some type of renal disease, but mutations in the ADH receptor gene or in the gene encoding aquaporin-2 • Excess secretion of ADH often results from ectopic production of ADH by malignant tumors elsewhere, referred to as the “syndrome of inappropriate secretion of ADH”

13. Oxytocin • Oxytocin is a nine amino acid peptide from hypothalamic neurons and transported to posterior pituitary for secretion into blood. Oxytocin is also secreted within the brain and from a few other tissues, including the ovaries and testes.  Oxytocin differs from antidiuretic hormone in two of the nine amino acids. • The term Oxytocin means “to stimulate birth”. Oxytocin acts on an estrogen-primed uterus. Pitocin, is used to induce labor.

14. Oxytocin in females mediates three major effects: Stimulation of milk ejection (milk letdown) Stimulation of uterine contraction at birth Establishment of maternal behavior: • Control of Oxytocin Secretion; • stimulus for release of hypothalamic oxytocin is initiated by physical stimulation of the nipples or teats.

18. Control of Oxytocin Secretion • A number of factors can inhibit oxytocin release, among them acute stress. For example, oxytocin neurons are repressed by catecholamines, which are released from the adrenal gland in response to many types of stress, including fright.

19. The hypothalamic releasing factors • Thyrotropin-releasing hormone(TRH) • Gonadotropin-releasing hormone (GnRH) • Corticotropin-releasing hormone (CRH) • Growth hormone-releasing hormone (GHRH) • Somatostatin • Prolactin release factor (PRF): • Dopamine (Prolactin release-inhibiting hormones)

20. Thyrotropin-releasing factor (TRF) • thyrotropin-releasing factor (TRF) or thyroliberin, • It consists essentially of three amino acids. Its basic sequence is glutamic • extraordinary array of functions. Some of which are: • a) It stimulates the secretion of thyroid-stimulating hormone from the pituitary. • b) It also affects the secretion of prolactin from the pituitary. • The TRH-secreting cells are subject to stimulatory and inhibitory influences from higher centers in the brain and they also are inhibited by circulating thyroid hormone.

21. Gonadotropin-releasing hormone (GnRH) • Also known as luteinizing hormone-releasing hormone (LHRH), is a peptide chain of 10 amino acids. • It stimulates the synthesis and release of the two pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). • Corticotropin-releasing hormone (CRH) • a large peptide consisting of a single chain of 41 amino acids. • It stimulates secretion adrenocorticotropic hormone (ACTH) in the corticotropin-producing cells (corticotrophs) of the anterior lobe of the pituitary gland. • Many factors, both neurogenic and hormonal, regulate the secretion of CRH. Among the hormones is cortisol, as part of the negative feedback mechanism. Vasopressin, the major regulator of the body's excretion of water, has an additional ancillary role in stimulating the secretion of CRH.

22. Growth hormone-releasing hormone (GHRH) • GHRH is a mixture of two peptides, one containing 40 amino acids, the other 44. • GHRH stimulates secretegrowth hormone (GH). • It is stimulated by stresses, including physical exercise, and secretion is blocked by a powerful inhibitor called somatostatin. • Negative feedback control of GHRH secretion is mediated largely through GH and growth factors generated by GH.

23. Somatostatin • Somatostatin is a mixture of two peptides, one of 14 amino acids, the other of 28. Somatostatin acts on the anterior lobe of the pituitary to • inhibit the release of growth hormone (GH) • inhibit the release of thyroid-stimulating hormone (TSH) • Somatostatin is also secreted by cells in the pancreas and in the intestine where it inhibits the secretion of a variety of other hormones.

24. Prolactin release factor (PRF): • released from the hypothalamus in a pulsatile fashion regulates the circulating level of prolactin. • Dopamine (Prolactin release-inhibiting hormones) • Dopamine is a derivative of the amino acid tyrosine. It mediates several functions in the brain, including • inhibiting the release of prolactin (PRL) from the anterior lobe of the pituitary; • The hypothalamic regulation of prolactin secretion from the pituitary is different from the hypothalamic regulation of other pituitary hormones in two respects: • The hypothalamus primarily inhibits rather than stimulates the release of prolactin from the pituitary. • This major inhibiting factor is not a neuropeptide, but rather the neurotransmitter dopamine.

27. Hormones of the anterior Pituitary gland The anterior pituitary hormones; The anterior lobe (or adenohypophysis) secretes hormones that regulate a wide variety of bodily functions. There are five anterior pituitary cells that secrete seven hormones: • composed of two distinctive parts: • The anterior pituitary; (adenohypophysis) is a classical gland composed predominantly of cells that secrete protein hormones. • The posterior pituitary (neurohypophysis)

29. Thank you