Physiology lec 2,3 NEW pitutary.pdf

Pituitary Gland (Hypophysis) Pituitary Gland (Hypophysis) Small gland 1 cm in diameter that lies in sella turcica. It is connected with the hypothalamus by the pituitary stalk (neck). It is divided into: 1-Anterior pituitary (adenohypophysis: glandular pituitary) It is composed of : 1-Anterior lo...

Pituitary Gland (Hypophysis) Pituitary Gland (Hypophysis) Small gland 1 cm in diameter that lies in sella turcica. It is connected with the hypothalamus by the pituitary stalk (neck). It is divided into: 1-Anterior pituitary (adenohypophysis: glandular pituitary) It is composed of : 1-Anterior lobe 2-Intermediate lobe 2-Posterior pituitary (Neurohypophysis) Anterior pituitary (Adenohypophysis) is the Master for majority of endocrine glands It controls: - Thyroid glands -Supra renal cortex -Gonads  Anterior pituitary secretes the following hormones: (1) Growth hormone: Somatotrophic hormone: Somatotropine: it is secreted by somatotropes (acidophils). (2) Prolactin: it is secreted by mammotropes (acidophils). (1) Thyroid stimulating hormone (TSH): Thyrotrophic hormone or thyrotrophine: it is secreted by thyrotropes (basophils). (2) Follicle stimulating hormone (FSH) & Luteinizing hormone (LH): gonadotrophic hormone or gonadotrophine: secreted by gonadotropes (basophils). (3) Adrenocorticotrophic hormone (ACTH): Corticotrophic hormone or corticotrophin: secreted by corticotropes (basophils).  Regultion Hypothalamic control Feed back control Stimulating Inhibitory Negative Positive factors factors feedback feedback Regulation of adenohypophysis function: Hypothalamic control (A) Hypothalamus releases stimulating factors or releasing factors: 1. Thyrotropine Releasing hormone (TRH). 2. Follicle stimulating hormone releasing hormone (FRH). 3. Luteinizing hormone releasing hormone (LHRH). 4. Corticotropin releasing hormone (CR). 5. Growth hormone releasing hormone (GRH). (B) Hypothalamus secretes inhibitory factors: 1. GH inhibitory hormone (GIH): called somatostatin 2. Prolactin inhibitory hormone: PIH (dopamine in nature) Feed back control: It is the mechanism by which the endocrine system tries to maintain the level of any hormone in blood nearly constant. [A]Negative feedback: the most common type e.g. if hormone level in blood is High, it stimulate endocrine gland to decrease its secretion and vice versa. According to distance between site of hormone secretion - & site of feedback effect, it is classified into: (a) Ultra short loop feedback :hormone suppress its own secretion e.g. hormone secreted from hypothalamus. (b)Short loop feedback: hormone suppresses its releasing factor e.g. hormone from anterior pituitary suppress its releasing factor from hypothalamus. (c)Long loop feedback: hormone secreted by endocrine gland affects hypothalamus & pituitary e.g. effect of cortisol on corticotropin releasing factor (CRF) from hypothalamus & ACTH from pituitary. (d)Long long loop feedback: e.g. hormone induces a metabolic response. Then the metabolic response suppresses the hormone release. [B] Positive feedback: less common If hormone increases in blood, it stimulates gland to produce more hormone from the gland e.g. Rise in estrogen leads to increase Luteinizing Hormone (LH) and further increase in estrogen.  Growth Hormone (GH) Chemistry: polypeptide Origin: acidophils of anterior pituitary Transport: 1. free form : 50 % 2. bound form: bound to growth hormone binding protein (GHBP) Level: the average/24 hours is 5-8 ng in child & 2-4 ng in adult 一 Functions of GH: Action on Growth: On protein metabolism: Anabolic On minerals On carbohydrate metabolism: On fat metabolism:  Action on Growth: increase size and number of cells On viscera: It stimulates hypertrophy (increase size of cells) & hyperplasia (increase number of cells). So, there is increase size of viscera On skeleton: It stimulates chondrogenesis→leading to growth of the epiphysial cartilage & elongation of bone (increase stature). After puberty, it increases thickness of all bones.  Mechanism: Effect of GH on growth is mediated by: Somatomedins Somatomedins: are polypeptides - secreted by liver and other tissues as cartilage. - They have insulin like action 1: stimulate oxidation of glucose 2: inhibit lipolysis -The insulin like action is not suppressed by anti-insulin antibodies.  * The principal circulating somatomedins are: 1/Insulin like growth factor I (IGF-I): Somatomedin C. It is produced by liver & chondrocytes. 2/Insulin like growth factor II (IGF - II): plays a role in fetal development. Factors that decrease somatomedins: 1. Protein deficiency. 2. Untreated diabetes. 3. Glucocorticoid.  On protein metabolism: Anabolic a) Increases protein synthesis. b)Positive nitrogen balance. c) Protein sparer Mechanism of its anabolic effect: Increases uptake of amino acids by cells, increases formation & activity of ribosomal RNA. On minerals Secondary to protein anabolism, GH causes mineral retention: a)Stimulates gastrointestinal absorption of Ca++ b)Decreases Na+ & K+ excretion On carbohydrate metabolism: GH is diabetogenic, it raises blood glucose level by: a) stimulating glycogenolysis & gluconeogenesis. b)Decreasing insulin receptors. Under high level of GH (e.g. GH secreting tumor) there is severe hyperglycemia.  On fat metabolism: GH is lipolytic and ketogenic: increase lipolysis & ketone bodies formation and fatty acid oxidation.  Control of GH secretion: Factors that increase GH secretion 1)Growth hormone releasing hormone GRH: It stimulates GH production from anterior pituitary 2)Insufficient calorie supply − Acute: decrease blood glucose & free fatty acids (FFA) − Chronic: fasting, starvation − Physical stress & Exercise 3)Increase circulating amino acids 4) Start of sleep 5) Hormones: Estrogen Factors that inhibit GH secretion 1- Growth hormone inhibiting hormone GHIH (Somatostatin): It inhibits GH production from anterior pituitary 2- Sufficient calorie supply - Acute: hyperglycemia & increase FFA - Chronic : obesity 3-Hormones: Cortisol & somatostatin Disorders of anterior pituitary: Decrease Deficiency of GH: Pituitary Dwarfism Deficiency of GH and gonadotropins: pituitary infantilism. Deficiency of all hormones: Panhypopituitarism: Pituitary cachexia Increase Gigantism: Increase GH before the closure of epiphysis of long bone (before puberty) Acromegaly: increase GH after closure of epiphysis (after puberty)  Deficiency of GH: Pituitary Dwarfism It is caused by decreased GH secretion before puberty Characters & features: 1- Development of all features are diminished in relative proportions: a-Arrested skeletal growth: ossification centers appear early and there is rapid union of epiphysis. b-Symmetrical growth retardation: the height (from crown to toes) = span (distance between outstretched fingers) & the distance from crown to symphysis = distance from symphysis to toes. C-Retardation of soft tissue growth 2- No mental retardation 3- Sexually normal Deficiency of GH and gonadotropins: pituitary infantilism Dwarfism is accompanied by hypogonadism & failure of sexual development.  Deficiency of all hormones: Panhypopituitarism: Pituitary cachexia: 1.Premature senility: Premature graying of scalp hair - loss of body hairs- Dry wrinkled skin- shrunken eye. 2.Pallor due to anemia & deficiency of ACTH & MSH (melanocyte stimulating hormone)  Gigantism: Increase GH before the closure of epiphysis of long bone (before puberty) Features: 1. Overgrowth of all bones leading to tall individual (with normal body proportions): growing period is lengthened; giant may continue to grow till time of death usually at 22 years. 2- Overgrowth of soft tissue: Visceromegaly 3- Hypogonadism due to pressure of acidophil on basophil. 4- Hyperglycemia: pituitary diabetes (insulin resistant) in  Acromegaly: increase GH after closure of epiphysis (after puberty) 1-Overgrowth of bones: the bones become thicker. Because of epiphysis fusion, there is only overgrowth of terminal portion of skeleton.  Acromegaly: increase GH after closure of epiphysis (after puberty) a- Overgrowth of bones of hands & feet. b- Overgrowth of vertebrae lead to bowing of spines or kyphosis  Acromegaly: increase GH after closure of epiphysis (after puberty) c- Overgrowth of skull: 1. Large & elongated. 2. Supra-orbital ridges are prominent 3. Nasal bones: thick 4. Overgrowth of mandible → protrusion of mandible & separation of teeth. 2- Overgrowth of soft tissues & muscles 3-Hyperglycemia and diabetes mellitus (25 % of cases): it is pituitary diabetes which is insulin resistant diabetes. 4-Diplopia and bitemporal hemianopia: in some cases as a result of compression on the optic chiasma which lies in front of the pituitary gland.  Prolactin Hormone Origin: Acidophils of anterior pituitary (lactotropes). Level in plasma: 8 ng/ml in female & 5 ng/ml in male. Functions in females: 1. Milk secretion from breast after estrogen & progesterone priming. 2. It increases action of mRNA for synthesis of milk casein & lactalbumin. 3. It has insulin like action on breast (stimulates glucose utilization & lipogenesis). 4. It prevents ovulation by inhibiting the effect of gonadotrophic hormones (FSH & LH) on ovaries. 5. It causes anovulation (infertility) & amenorrhea during lactation. Functions in male: enhance LH receptors in leydig cells to increase testosterone hormone. ▪ Control (Regulation) of prolactin: (1)Hypothalamus: Prolactin is under tonic inhibition by hypothalamus. Hypothalamus secretes prolactin inhibitory hormone (PIH) which is dopamine in nature. (2)Negative feedback: High level of prolactin stimulates prolactin inhibitory hormone (PIH)from hypothalamus (dopamine) to decrease prolactin secretion. (2)Sleep: prolactin rises at onset & persists at plateau. (3)Stress: e.g. exercise & surgery. (4)Suckling: causes rise with each nursing. (5)Pregnancy: it rises gradually to a peak at time of parturition. (6)Parturition: it falls to original level 8 ng/ml (7)Dopamine Receptor Blockers (antagonists): chloropromazine stimulate prolactin. While dopamine & dopamine agonists (Bromocryptine) decreases PRL. ▪ Disturbances of PRL secretion: (A) Hypoprolactinemia: rare. (B) Hyperprolactinemia: Cause: (1) Tumor of anterior pituitary: It secretes prolactin (2) Dopamine blocking agents e.g. chloropromazine. * Effects: it is a common cause of gonadal dysfunction because PRL inhibits effects of gonadotrophins on gonads. In female: infertility, amenorrhea, galactorrhea & decrease libido. In male: infertility, impotence, gynecomastia, decrease libido Treatment: Dopamine agonist (stimulating) drugs e.g. Bromocryptine. Posterior Pituitary It releases 2 hormones: (1)Vasopressin: Antidiuretic hormone (ADH) (Pressophysin) (2) Oxytocin: Pitocin (Oxyphysin). o Origin: Their precursors are manufactured in supra- optic & paraventricular nuclei in hypothalamus. o Storage: They are packed in secretory granules o Inactivation: in kidney & liver by vasopressinase & oxytocinase. Antidiuretic hormone (ADH) (Vasopressin) ▪ Origin: mainly supraoptic nuclei & to a lesser degree paraventricular nuclei. ▪ Chemistry: nanopeptide i.e. 9 amino acids. ▪ Functions: Through ADH receptors which are 3 types: 1-V1: in vascular smooth muscles. 2-V2: in renal tubules. 3- V3: in corticotropes of anterior pituitary. Renal effects: a) It helps facultative water reabsorption in late distal tubules of kidney via V2 receptors (decrease H2O loss). b)It enhances K+ secretion. c) It acts on V3 receptors in glomerular mesangium increasing prostaglandin E2 (PGE2) which is vasodilator. - ADH-PGE2 vasodilator antagonizes ADH- vasoconstrictor effect maintaining renal perfusion. Extra-renal effects: a- Vascular system: ADH in large dose causes vasoconstriction (VC) leading to increase arterial blood pressure. Thus, it has a pressor effect in hemorrhage & shock. It cause constriction of visceral blood vessels & used to stop gastrointestinal bleeding. *Mechanism: it acts on V1 receptors b- Anterior pituitary: - It stimulates V3 receptors of corticotropes to increase ACTH. - CRH is co-secreted with ADH from paraventricular nuclei. It stimulate ACTH & cortisol to antagonize stress. c- On brain: help memory. d- It has 10 % of oxytocin action. Control (regulation) of ADH secretion: [A] Factors Increase ADH: (1) Increase plasma osmolarity: Increase osmotic pressure of plasma 1% stimulates osmoreceptors in hypothalamus & ADH secretion. ADH stimulates water reabsorption & osmolarity return to normal. (2) Hypovolemia: decrease blood volume by 10% affect ADH through Arterial baroreceptors Volume atrial receptors Renin – angiotensin system.  (3)Stress: through CRH-ADH system (4)Nausea: stimulates ADH (unknown mechanism) )5)Drugs: morphine, nicotine. (6)Hot weather. [B] Factors Decrease ADH: Low osmolarity – Hypervolemia –alcohol & cold. ADH deficiency (diabetes insipidus) ▪ Cause: 1-Damage of neurohypophyseal system 2-Nephrogenic diabetes insipidus: inability of kidney to respond to ADH due to absence of receptors (V2). Symptoms: 1.Polyuria: large volume of urine up to 10 liter /day. -Low specific gravity of urine (1002 – 1003). -Loss of H2O soluble vitamins & electrolytes. -Tasteless urine (insipidus). 2-Polydipsia: drinking large volume of fluid. 3-Basal Metabolic Rate (BMR): increases as more volume of water are heated. Oxytocin (Pitocin)  Oxytocin (Pitocin) ▪ Functions: (1)Milk ejection (milk letdown): Most important It contracts myoepithelial cells around breast alveoli. Milk is squeezed out of alveoli into ducts & baby obtains it by suckling. (2)Uterine contraction: during labor to expel baby & placenta (3)During sexual intercourse : In male: contraction of vas deferens to ejaculate semen. In female: contraction of myometrium to help sperm transport. ▪ Control :Neurohormonal reflex (a)Suckling reflex: suckling stimulates touch receptors in the nipple to cause reflex secretion of oxytocin. (b) labor: cervical stimulation by the head of the fetus during labor causes reflex secretion of oxytocin. (c)Sexual intercourse: stimulation of female genital tract sends impulses which cause oxytocin secretion.