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ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 Anatomy of Hypothalamus, pituitary & pineal gland Hypothalamus The hypothalamus is a part of the diencephalon, lying below the thalamus and its weight is about 4 gm weight, i...

ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 Anatomy of Hypothalamus, pituitary & pineal gland Hypothalamus The hypothalamus is a part of the diencephalon, lying below the thalamus and its weight is about 4 gm weight, it is the link between the nervous system and the endocrine system via the pituitary gland. Pineal Gland (Epiphysis Cerebri) It is a part of epithalamus which is a part of diencephalon. It is a neuroendocrine gland that secretes melatonin hormone which modulates the sleep-wake cycle by controlling the circadian rhythm. Position and relations The pineal gland projects from the posterior wall of the 3rd ventricle below the splenium of corpus callosum. It is attached to the rest of the brain by the pineal stalk. Shape and measurements: The pineal gland is conical in shape and its weight is about 0.1 gm. Development: It develops at end of 4th week of prenatal life, as an outward projection from the posterior wall of the 3rd ventricle. Blood supply It is supplied by the posterior choroidal arteries (from the posterior cerebral artery) and drains into the internal cerebral veins. Pituitary Gland (Hypophysis Cerebri) The pituitary gland is a major gland of the endocrine system. It secretes hormones that control the actions of other endocrine organs. Position: 14 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 It lies within the hypophyseal fossa of the sphenoid bone, where it is covered superiorly by a reflection of the dura mater – the diaphragma sellae. The latter is pierced centrally by an aperture for the infundibulum (pituitary stalk) connecting it with the hypothalamus. Shape and measurements: It is a pea-sized oval structure, about 12 mm in transverse and 8 mm in anteroposterior diameter, and with an average adult weight of 500 mg. Relations: * Superiorly– diaphragma sellae, optic chiasma. * Anteriorly – tuberculum sellae * Posteriorly – dorsum sellae * Inferiorly – sphenoid air sinus * Laterally – cavernous sinus. Coronal (A) and sagittal (B) sections through the middle A cranial fossa showing relations of pituitary gland B Subdivisions and development: The pituitary gland is a ‘’two-in-one’’ structure consisting of the anterior pituitary and the posterior pituitary. These parts have different embryonic origins and function very differently. Anterior Pituitary (adenohypophysis): is derived from an upward growth of the roof of the primitive mouth called Rathke’s pouch. The lobe can be further divided into three parts: ✓ Pars distalis 15 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 ✓ Pars intermedia ✓ Pars tuberalis Posterior Pituitary(neurohypophysis): develops as a downgrowth from the floor of the diencephalon. It is connected with the hypothalamus by the infundibulum. Parts of hypophysis cerebri as seen in sagittal section Blood Supply: Hypothalamic-hypophysial Portal System This system connects the hypothalamus and the anterior pituitary gland. It consists of two capillary plexuses—one in the hypothalamus and the other in the anterior pituitary. In the hypothalamus there is a 1ry capillary plexus from which blood drains into a portal vein which enters the anterior pituitary to form a 2ry capillary plexus before draining into the venous circulation. This system allows the hormones-releasing factors released in the capillaries of the hypothalamus to be carried out to the anterior pituitary to stimulate it to release appropriate hormones. 16 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 Arterial Supply The following branches of internal carotid artery supply the pituitary gland 1. Superior hypophyseal artery, one on each side. 2. Inferior hypophyseal artery, one on each side. Venous Drainage Short veins from the pituitary gland drain into neighboring dural venous sinuses (e.g., cavernous and intercavernous sinuses). The hormones pass out of the gland through venous blood to the target sites. Symptoms due to pressure of pituitary adenoma on adjacent structures: – Enlargement of hypophyseal fossa due to downward growth (intrasellar growth) of an adenoma. It is seen as ballooning of hypophyseal fossa (sella turcica) in plane radiograph of skull (lateral view). – Bitemporal hemianopia (loss of vision in right and left temporal fields of vision) due to the upward growth of adenoma pressing the central part of the optic chiasma. 17 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 Histology of pineal gland and pituitary gland Pineal Gland (Epiphysis Cerebri) Histologically it is formed of: Stroma: o Capsule: The gland is enclosed by pia matter. o Trabeculae: A very thin connective tissue septa descend from the capsule subdividing the gland into indistinct lobules. o Reticular fibers: They form fine reticular fibers network. Parenchyma: o Two types of cells are forming the parenchyma of the gland: ▪ Pinealocytes. ▪ Interstitial cells. Pinealocytes: - The main cells contained in the pineal gland. - They are modified neurons. LM: - They are arranged in cords and clumps separated with blood vessels. - They are large branched cells. - Large spherical or lobulated nucleus with prominent nucleolus. - Pale basophilic cytoplasm. EM: - Many mitochondria. - Small Golgi complex, RER, SER and secretory vesicles. - Large numbers of cytoplasmic processes. Function: Secrete melatonin hormone. Interstitial cells - They are present among pinealocytes constitute about 5 of the cells. - They are modified astrocytes neuroglial cells. - They have long cytoplasmic processes. o In addition to the two cell types, the human pineal gland is characterized by presence of extracellular calcified concretions called brain sands or corpora arenacea. They increase in size and number with advancing age. Their significance is unknown. 18 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 Pituitary gland (Hypophysis Cerebri) Parts of hypophysis cerebri as seen in sagittal section Histologically:  The hypophysis composed of two different lobes: ✓ Adenohypophysis or anterior pituitary ✓ Neurohypophysis or posterior pituitary  Both lobes differ in their embryonic origin. Therefore, the two lobes have distinctly different morphology and function.  ADENOHYPOPHYSIS  It is the glandular epithelial part of the pituitary. It appear deeply stained with H&E.  It is divided into 3 parts: Pars distalis Pas tuberalis Pars intermedia Pars Distalis The pars distalis is the largest portion. It is formed of: Stroma: Very thin connective tissue capsule. Delicate reticular fibers support sinusoids and blood vessels. Parenchyma: Irregular cords or clusters of secretory endocrine cells. Irregular blood sinusoids. Cells of pars distalis are classified according to staining affinity into: ✓ Chromophobes. 19 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 ✓ Chromophils. o Chromophobes: They constitute 50% of epithelial cells. They have poor affinity for staining because the cytoplasm contains few granules. They are a reserve cells which can differentiate to other types of chromophils. o Chromophils: They constitute 50% of epithelial cells. They have intense affinity for staining because of the abundant content of hormones in their secretory granules. Accurate identification of different chromophils is given by electron microscope examination and immunohistochemistry using antibodies against the hormone products. According to the staining they are classified into: A. Acidophils. B. Basophils Acidophils Two types of acidophils are present: Somatotrophs Mammotrophs Somatotrophs They are most numerous type of cell population. They are responsible for the secretion of somatotropin (growth hormone). Mammotrophs (Lactotrophs) In males and nulliparous (no pregnancy) females, they constitute approximately 9% of the cell population. They reach up to 31% of the adenohypophyseal cells in multiparous (multiple pregnancy) females. They secrete prolactin. They distributed individually not in clusters or cords. LM: Acidophils are more in number (40) and smaller in size. Both types of acidophils have: They are large rounded cells with central rounded nucleus and acidophilic cytoplasm. Negative periodic acid-Schiff (PAS) reaction. They give positive orange G stain. 20 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 EM: Both cell types can differentiated by their ultrastructure features as following: Ultrastructurally somatotrophes have: Large euchromatic nucleus with prominent nucleoli. Many cisternae of RER parallel to cell surface. Well-developed Golgi apparatus. Small rod shape mitochondria. Numerous, rounded, electron dense granules (300-350 nm in diameter) were distributed in their cytoplasm. 2-Ultrastructurally mammotrops have: Few elongated cisternae of ER and Golgi apparatus. During pregnancy; RER become highly developed, parallel cisternae in peripheral cytoplasm and Golgi approach nuclear size. Large dense granules vary from (500 to 900 nm in diameter). Abundant lysosomes. Basophils Three types of basophils are present: Thyrotrophs Corticotrophs Gonadotrophs LM of the three types: Basophils are less in number (10) and larger in size. They are polygonal cells with eccentric rounded nuclei. Basophilic cytoplasm. 21 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 Positive periodic acid-Schiff (PAS) reaction because of high content of glycoprotein. They give negative orange G stain. EM of the three types: Large euchromatic nuclei with prominent nucleoli. Cytoplasm contains few dilated rER cisternae, well developed Golgi and mitochondria. Thyrotrophes are located not close to sinusoids. They have the smallest secretory granules (150 nm diameter) arranged along the cell periphery. Gonadotrophes are located close to sinusoids. They have variable sized secretory granules within the same cell (200-400 nm diameter). Corticotrophes have the least abundant granules. Thyrotrophs They account about for 5% of adenohypophyseal cells. They secrete thyroid-stimulating hormone (TSH) or thyrotropin which stimulates the thyroid to release T3 (triiodothyronine) and T4 (thyroxine) into the blood stream. Corticotrophs They represent approximately 15 - 20% of adenohypophyseal cells. The target cells are cells of zona faciculata and zona reticularis of adrenal cortex. 1) The corticotrophs secrete mainly adrenocorticotropic hormone (ACTH). 2) ACTH stimulates the adrenal glands to release glucocorticoids in response to stress as anxiety, thirst or injury. 3) Corticotrophs also secrete gonadocorticoids. Gonadotrophs They represent approximately 10% of adenohypophyseal cells. They secrete follicle-stimulating hormone (FSH), interstitial cell stimulating hormone (ICSH) and luteinizing hormone (LH). In females: FSH stimulates growth of ovarian follicles. LH stimulates ovulation and development of corpus luteum. In males: FSH stimulates Sertoli cells, activating and promoting spermatogenesis. ICSH simulates production of testosterone by the interstitial cells of the testis. Folliculo-stellate cells They constitute a considerable population of non secretory cells. They are located between the secretory cells in the anterior pituitary. They form a network of communication system through gap junctions between the cell processes by which information is transferred throughoutthe gland. 22 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 Pars Tuberalis It is upward extension of the anterior lobe. It is the most highly vascular part of the pituitary gland. Cells are arranged in cords or follicles near to blood vessels. They are basophilic cuboidal cells with few granules, glycogen and multiple lipid droplets. Its function is unknown but they are suggested to secret FSH and LH. Pars Intermedia In human, pars intermedia are not well-developed. It is formed of polygonal basophilic cells which are arranged in cords or follicles with central faintly-stained colloidal acidophilic material. The cytoplasm is rich in mitochondria and contains small secretory granules of variable electron densities (200-250 nm diameters). In amphibians and reptiles, the cells of pars intermedia secrete melanocyte stimulating hormone (MSH) which stimulates the synthesis of melanin pigments by melanocytes. In human, this hormone is secreted by some basophils cells which are present in the pars distalis of the anterior pituitary.  NEUROHYPOPHYSIS  It is the nervous part of the pituitary. It appear pale stained with H&E as it contains nerve fibers with no glandular secretory cells and no nerve cells.  It includes 3 parts: Median eminence Infundibular stems Pars nervosa Pars Nervosa It secretes antidiuretic hormone (ADH) and oxytocin. It contains nerve fibers, pituicyte, accumulation of secretion (Herring's bodies) and blood sinusoids (discontinuous or sinusoidal capillaries). Nerve fibers They are unmyelinated axons of specialized secretory neurons in the supraoptic and paraventricular nuclei of the hypothalamus. They form hypothalamo-hypophyseal tract which end in pars nervosa. Pituicytes They are highly branched cells. They contain no secretory granules. 23 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 They are supportive like neuroglial cells. Herring's bodies They are neurosecretory granules accumulation at the axonal terminals with their contact blood capillaries. They contain antidiuretic (vasopressin) and oxytocin hormones secreted by the secretory nerve cells, which are present in the supraoptic and paraventricular nuclei of the hypothalamus. Blood sinusoids: They are network of wide fenestrated sinusoids. MICROCIRCULATION OF PITUITARY GLAND (Hypophyseal Portal Circulation) There are two groups of arteries supplying the hypothalamus and the pituitary gland: Several Superior Hypophyseal Arteries: They arise from the internal carotid. They anastomose freely around the median eminence. They supply the hypothalamus, median eminence, infundibular stalk and the pars distalis. Capillaries arise from these vessels form primary plexus in the median eminence. These capillaries drain into large venules called portal veins. These portal veins course downward around the hypophyseal stalk to an extensive network of thin walled sinusoids within the pars distalis of the anterior pituitary called secondary capillary plexus. The venules connecting the primary plexus to secondary plexus constitute hypophyseal portal circulation. This special vascular connection enables the secreted hypothalamic hormones to reach the anterior pituitary directly in order to regulate the functions of the secretory cells of the anterior pituitary. Two inferior hypophyseal arteries: They are branches of internal carotid artery They supply mainly the pars nervosa and to a less branches to pars distalis. The venous blood from both pituitary lobes drains into the cavernous sinus through a number of venous channels. 24 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 25 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 Physiology of Pituitary gland As mentioned before, Pituitary or hypophysis is a small gland about 1 cm in diameter. - Lies in the Sella Turcica at the base of the brain connected to the hypothalamus by the hypophyseal stalk. It is divided into anterior, intermediate & posterior parts. Functions of pituitary Gland: 1. Posterior Pituitary (Neurohypophysis): Posterior pituitary Hormones: - Vasopressin (Antidiuretic hormone, ADH) - Oxytocin 2. The Intermediate Lobe = PARS INTERMEDIA -The Intermediate lobe in human is rudimentary & no hormones is secreted in adults. - It secretes the Melanocyte stimulating hormone (MSH) which causes spreading of melanin pigment in melanocytes -ACTH causes the same effect as MSH (the cause of pigmentation in Addison's disease) 3. Anterior Pituitary (Adenohypophysis) -It is called “Master Gland” (makes & secretes various trophic hormones) -Trophic Hormones: act on other endocrine glands to stimulate release of their hormones Secretion of Hypothalamic factors: The neurons from various parts of the hypothalamus send fibres into the median eminence which secretes polypeptide hormones (hypothalamic hormones) that are absorbed into the hypothalamo-hypophyseal portal vessels to be carried to the adenohypophysis. They control the release of adenohypophyseal hormones. They are releasing or inhibitory factors according to their function : Thyrotropin Releasing Factor (TRF) Corticotropin Releasing Factor (CRF) Gonadotropin Releasing Factor (GRF) Somatotropin Releasing Factor (SRF) Somatostatin (Growth hormone inhibiting factor) Prolactin Inhibitory Factor (Leutropin inhibitory factor, LIF) 26 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 Hormones of Anterior Pituitary 1- Thyroid Stimulating Hormone (TSH) 2- Adrenocorticotrophic Hormones (ACTH) 3- Gonadotrophic Hormones 4- Follicle Stimulating Hormone (FSH) 5- Luteinizing Hormone (LH) 6- Growth Hormone (GH) 7- Prolactin (PRL) Thyroid stimulating hormone (TSH, Thyrotropin) : Functions: 1- It stimulates the development of the thyroid gland, helps its growth and increasesvascularity. 2 - It also stimulates the process of thyroxine formation. Adrenocorticotrophic hormone (ACTH) -Corticotropin : Functions: 1- It stimulates the development of the adrenal cortex. 2- It stimulates the formation and secretion of all the adrenal cortex hormones except aldosterone hormone. 3- It has a fat mobilizing effect 4- It has melanocyte-stimulating effect. Control: 1- Feedback mechanism : increase in adrenocortical hormones level in blood → inhibits ACTH secretion directly on the anterior pituitary and through inhibition of the hypothalamus. 2- Stress: emotional stress stimulate the hypothalamus to secrete corticotropin - releasing factor to stimulate ACTH secretion. 3- ADH : stimulates corticotrophin release Gonadotrophins: A- Follicle-stimulating hormone (FSH) B- Luteinizing hormone (LH) 27 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 Growth hormone (GH) Somatotropin It is a polypeptide hormone formed of 191 amino acids with a molecular weight of 22,000. The growth hormone is metabolized rapidly in the liver which is responsible for itsduration of action (20 minutes). Functions of Growth hormone : This hormone stimulates growth of all tissues of the body. It increases the size and numberof the cells by: 1- Increases the rate of protein synthesis: –It causes protein accumulation in all cells of the body by enhancement of amino acids transport through the cell membrane. –This results in decreased amino acid blood level –It increases transcription of DNA to form RNA. –It stimulates RNA translation in ribosomes. 2- Lipolytic and Ketogenic effect : -It increases mobilization of fatty acids and increases the use of fatty acids for supplying energy. -So, excess growth hormone → ketosis 3- Decreases utilization of carbohydrate for energy production: -It decreases the use of glucose for energy production as a result of increased utilization of fatty acids for energy (large amount of acetyl- CoA blocks glucose breakdown). -It depresses uptake of glucose by the cells , so it increases the blood glucose level up to 100% = anti-insulin effect (diabetogenic effect). -Inhibits hexokinase enzyme, so decreases glucose uptake by muscles. -Increases hepatic glucose output. -It increases insulin release from pancreas (over stimulation) that causes burn out of the beta cells of the pancreas. 4- It increases calcium absorption from the G.I.T. 5- It causes reabsorption of Na+ , K+, Ca++, PO4--, and C1- from the kidney and so ,helping bone matrix formation. 28 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 6- Chondrogenesis and Bone Growth : In young subjects in which the epiphysis have not yet fused to the long bones, growth hormone stimulates chondrogenesis (proliferation of epiphyseal cartilage), and as the cartilaginous epiphyseal plates widen, they lay down more matrix at the end of long bones with stimulation of osteoblastic activity (bone forming cells) → increased length of long bones. In adult subjects in which the epiphysis are closed, thus the linear growth is impossible. Control of Growth hormone secretion: * Feedback Mechanism: ✓ Hypoglycaemia and increased amino acid concentration in blood stimulate therelease of G.H. ✓ Growth hormone feedbacks to inhibit its own secretion. * Hypothalamus: ✓ It secretes a Somatotropin- releasing factor (SRF) which stimulates the release of GH. Cellular depletion of proteins enhances SRF secretion (to correct the protein deficiency) beside stressful stimuli. ✓ The hypothalamus also releases the inhibitory factor, Somatostatin. * It is also released by exercise, stress andglucagon and Ghrelin hormone. 29 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 1. Mechanism of Action of Growth Hormone : - G.H. acts on the liver to produce Somatomedin C (IGF-1 or sulfation factor, as it stimulates the incorporation of sulfate into the cartilage), - Somatomedin C induces growth promoting activities in many tissues as cartilage with a prolonged duration of action (20 hours). Prolactin hormone It is one of the hormones of the anterior pituitary gland, secreted by the Lactotroph cells (alpha cells). It is a protein consists of 170 amino acids with a molecular weight of 25.000. Control of secretion: 1. Hypothalamic control: -The hypothalamic effect is mainly inhibitory. -Two hypothalamic factors for prolactin regulation: a-Prolactin Release Inhibiting Factor: -Dopamine (tonic inhibition) -others as Gamma Amino Butyric acid (GABA), Gonadotrophin associated peptide (GnAP). b-Prolactin Releasing Factors: -Thyrotrophin releasing hormone (TRH) - vasoactive intestinal peptide(VIP) - Peptide Histidine Isoleucine (PHI) 2. Hormonal control: a-Thyroxine → inhibits prolactin secretion via -ve feedback, decreases number of TRH receptors on lactotrophs. b-Estrogens → stimulate the release of prolactin via: i- increase the number of TRH receptors on the lactotrophs 30 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 ii-stimulate lactotrophs to secrete prolactin. iii- increase proliferation of lactotrophs. 3. Prolactin secretion is increased also during: sleep Severe exercise Stress Sexual stimulation Normal Level of Prolactin: 1. The normal level of prolactin is 10-25 ng/ml with diurnal variation in which the peak level occurs 4-5 hours after the onset of sleep. 2. During pregnancy, prolactin levels rise to high concentrations (reach 200-400 ng/ml at term) 3. This is due to increase in estrogen secretion from the placenta. 4. In non-breast-feeding woman, prolactin level returns to normalnon pregnant level in 7 days after delivery. 5. In breast-feeding woman prolactin level decline to ~ 50% (100 ng/ml) within the 1st week postpartum, suckling increases the prolactin level to 400-800 ng/ml Functions of prolactin: - It is the principal hormone that stimulates milk formation (formation of the primary protein, Casein). - It inhibits ovulation by blocking the effect of gonadotropic hormone on ovaries. This is the cause of amenorrhea during lactation. - It has general metabolic functions similar to those of GH. e. g. diabetogenic. - During pregnancy, the high level of prolactin stimulates breast growth, however, no lactation occurs. *- Lactation is inhibited during pregnancy by progesterone (secreted from the placenta) which interferes with prolactin action at the receptor sites on the alveolar cells of mammary glands. *- After delivery The rapid disappearance of progesterone allows prolactin to stimulate milk formation. N.B.: -Luteotropic = maintains corpus luteum. -Prolactin stimulates milk secretion from already formed mammary glands prepared by estrogen and progesterone. Posterior Pituitary (Neurohypophysis) functions Formation and release of posterior pituitary hormones: 31 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 Two polypeptide hormones; ADH (Vasopressin) & Oxytocin (formed of 9 aa). ADH is formed in the cells of the supraoptic nuclei & Oxytocin is formed from paraventricular nuclei of hypothalamus. a) Their precursor molecules called Neurophysin that include: I- Preprooxyphysin → Oxyphysin or Neurophysin I → oxytocin. II- Prepropressophysin →Pressophysin or Neurophysin II → Vasopressin. b) -Then they are transported as granules by axoplasmic flow to the nerve endings in the posterior pituitary, where they are stored as Herring bodies. -They are released by nerve impulses from hypothalamus (by help of Ca++ ions ) 1) Vasopressin (ADH) Receptors of vasopressin (Antidiuritic hormone) V1A receptors: in blood vessels mediates vasoconstrictor effect V1B receptors: in anterior pituitary mediates ACTH secretion ✓ Both of them act by increasing intracellular Calcium. V2 receptors: Found in the nephrons (thick part of the loop of Henle, DCT & CD). ✓ Mediate the antidiuretic effect ✓ They act by activation of adenyle cyclase and increasing cAMP. Functions of ADH: 1- Antidiuresis (decreases excretion of water by the kidneys): ↑↑ permeability of distal convoluted tubules (DCT) & collecting ducts (CT) to water → ↑↑ water reabsorption. Mechanism of action: ADH bind to receptors on the blood side membrane of the tubular cells → + + adenyl cyclase → formation of cAMP → + + protein kinase → ↑ formation of microtubules in the cell membrane → ↑ permeability of the luminal side of the cell membrane to water. Vasoconstrictor effect: ADH has no effect on blood vessels in normal conditions. But in large dose produce VC all over the body except cerebral & renal blood vessel. 32 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 Decrease blood volume by 10 % is sufficient to release enough ADH to cause VC to control blood pressure. 2- Contraction of smooth muscles: intestinal wall, bile duct & uterus. 3- ADH inhibits renin release. 4- ADH stimulates Corticotrophin (ACTH) release from the anterior pituitary. Regulation of ADH secretion 1) Osmotic Regulation: -↑ osmotic pressure of the blood → ++ osmoreceptors (AV3V Region in hypothalamus) → impulses via the hypothalamo-hypophyseal tract → ↑ release ADH. - ADH → ↑ H2O reabsorption while electrolytes continue to be lost → dilutes theextracellular fluids → restore normal osmotic pressure. - Dilution of extracellular fluids (↓osmotic pressure) inhibits ADH secretion -Na+ & mannitol are potent stimulators of ADH 2) Effective Plasma volume: -Volume receptors (as in atria) normally send tonic inhibitory impulses to supraopticnuclei to decrease ADH. c) Increase plasma volume → + + these receptors → ↑inhibitory effect on the supra- optic nuclei → ↓↓ ADH release from posterior pituitary. 3) Decrease plasma volume (as in haemorrhage) → ↓ inhibitory impulses from the volume receptors→↑↑ release of ADH→ water retention → ↑ extracellular fluid (ECF) volume back to the normal. 4) Angiotensin II: Angiotensin II → ↑ ADH secretion. Angiotensin II ↑↑ size or number of Na+ channels in osmoreceptors→ ↑ Na+ influx→ depolarization→ ↑↑ rate of firing of action potentials in hypothalamo-hypophyseal tract → ↑↑ ADH. 5) Pain, trauma, anxiety & nicotine→ ↑ ADH. 6) Alcohol :↓↓ ADH secretion → marked diuresis. 33 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 2) Oxytocin: Functions of oxytocin: Effect on the Uterus: it stimulates the pregnant uterus (during labour) → causes powerful contraction. Effect in primary fertilization of the Ovum: Sexual stimulation during intercourse causes reflex stimulation of the paraventricular nuclei → ↑↑ oxytocin → uterine contractions (orgasm) → uterine suction of semen upward toward the fallopian tubes. Effect on milk ejection: Oxytocin causes contraction of the myoepithelial cells around the alveoli of the mammary glands→ milk ejection (let down). Help sperm transport during ejaculation: as it increases the contractility of the vas deferens & seminal vesicle. 34 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 Regulation of oxytocin secretion: 1- Dilatation (stretch) of the uterus, cervix & vagina during labor→ ++ stretchreceptors → + + paraventricular nuclei → ↑↑↑ oxytocin→ ↑↑↑ uterine contraction → labour. 2- Stimulation of the vagina & uterine cervix (during intercourse)→ impulses via sensory nerves to paraventricular nuclei → hypothalamo-hypophyseal tract → ↑↑oxytocin output (Ferguson Reflex). 3- Suckling of the nipple → sends impulses through sensory nerves (3rd ,4th& 5th thoracic nerves)→ paraventricular nuclei → ↑↑↑ oxytocin (Suckling Reflex). 4- Opioid peptides (Endorphins) → ↓↓ oxytocin release (so stress, fear & anger inhibit milk output in lactating women). 35 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 Physiology of Pineal Gland I-Characters of Pineal Gland - The pineal gland is a secretory neuroendocrine organ, located outside the blood-brain barrier. - Connected to the posterior wall of the third ventricle of the brain in a groove where the two thalamui join. - It receives the second most profuse blood supply in the body, next to the kidney. - The pineal gland is mainly known to produce a single hormone, melatonin. II-Secretion of Melatonin 1) Melatonin is synthesized within the pinealocytes from tryptophan. 2) It is synthesized in other sites of the body (skin, gastrointestinal tract, retina, bone marrow, placenta) acting in an autocrine or paracrine manner. 3) Melatonin modulates our sleep and waking patterns by affecting different cells within the brain and body. 4) Melatonin has a key role in establishing our circadian rhythm, which is the twenty-four-hour cycle of our bioactivity that matches the solar cycle of the day. ▪ Melatonin, secreted only during the dark period of the day, is a marker of the phase of the internal circadian clock. ▪ At birth, melatonin levels are almost undetectable. ▪ A melatonin rhythm appears around 2 to 3 months of life, levels increasing exponentially until a peak in prepubertal children; melatonin concentrations in children are associated with Tanner stages of puberty. II-Functions of Melatonin 36 ENDOCRINE & REPRODUCTIVE SYSTEM MODULE 2024-2025 ▪ Regulation of many reproductive processes such as puberty, gonadal function, and pregnancy. ▪ Has an inhibitory influence on the hypothalamic secretion of GnRH in humans. ▪ Plays a role in circadian thermoregulation. Melatonin peak is associated with the lowest diurnal body temperature, together with maximum tiredness, lowest alertness and performance. ▪ Regulation of energy metabolism and glucose homeostasis. ▪ Anti-oxidant, anti-aging and antitumor activities. Main function of melatonin 37