2- Pituitary.pdf

Pituitary Gland  Pituitary gland ❖Found at the base of the brain in the Sella turcica within the sphenoid bone. ❖Connected to the hypothalamus by the pituitary stalk ❖“The Master Gland” as it controls the secretion of other glands. ❖Its secretion is controlled by the...

Pituitary Gland  Pituitary gland ❖Found at the base of the brain in the Sella turcica within the sphenoid bone. ❖Connected to the hypothalamus by the pituitary stalk ❖“The Master Gland” as it controls the secretion of other glands. ❖Its secretion is controlled by the hypothalamus.  Lobes of Pituitary A. Posterior Pituitary Neurohypophysis; Has neural connection with hypothalamus. Derived embryologically from the third ventricle of the brain. B. Anterior Pituitary, Adenohypophysis; Has vascular connection with hypothalamus. Derived embryologically from invagination of cells from the oral cavity (Rathke’s pouch).  Hormones of Pituitary Basophils 1.TSH: Thyroid-stimulating hormone 2.ACTH: Adrenocorticotropic 3.FSH: Follicle-stimulating hormone 4.LH: Luteinizing hormone 1.Oxytocin. 2.ADH: Antidiuretic hormone. Posterior Neurophysin; a preprohormone released Acidophils concurrently with oxytocin or ADH.v 1.GH: growth hormone 2.PL: prolactin  Cells of Anterior Pituitary The anterior pituitary gland contains several different cell types that synthesize and secrete hormones. 1. Somatotropes; human growth hormone (hGH) 50% of cells in the anterior pituitary secrete growth hormone 2. Corticotropes; adrenocorticotropin (ACTH) 3. Thyrotropes; thyroid-stimulating hormone (TSH) 4. Lactotropes; prolactin (PRL) 5. Gonadotropes; gonadotropic hormones, which include: Luteinizing hormone (LH) Follicle stimulating hormone (FSH) Hypothalamus Integrates the activities of the endocrine system and the nervous system Secretes releasing and inhibitory hormones that regulate the secretion of anterior Pituitary gland. Secretion from the posterior pituitary is controlled by hypothalamic nerve signals. Secretion by the anterior pituitary is controlled by hormones: hypothalamic releasing and inhibitory hormones conducted through hypothalamic-hypophysial portal vessels Hypothalamus receives signals from many sources in the nervous system to controls and integrates the activities of the nervous and endocrine systems Secretion of ant. pituitary is under hypothalamic hormonal control Effect on anterior pituitary Hypothalamic hormone gland Thyrotropin releasing hormone (TRH) ? Corticotropin releasing hormone (CRH) ? Gonadotropin releasing hormone (GnRH) ? Prolactin-inhibiting hormone (dopamine) Growth hormone inhibitory hormone (GHIH) ? Growth hormone releasing hormone (GHRH) ? 7 Hypothalamic hormone Effect on anterior pituitary gland Thyrotropin releasing hormone (TRH) release of TSH Gonadotropin releasing hormone (GnRH) release of LH and FSH Growth hormone releasing hormone (GHRH) release of GH release of ACTH Corticotropin releasing hormone (CRH) Growth hormone inhibitory hormone (GHIH) inhibition of GH (somatostatin) prolactin-inhibiting hormone (dopamine) Inhibition of prolactin 8 Hormones of Anterior Pituitary  Growth hormone (GH) Actions: ➔ Promotion of growth; it increases the size and number of cells 1. ↑Rate of protein synthesis & deposition → anabolic & produces a positive nitrogen balance. 2. Promotes utilization of energy: Fat: Mobilization of fatty acids from adipose tissues (lipolysis). Carbohydrate: diabetogenic ↑ blood glucose → ↑in insulin secretion ➔ Insulin resistance. ▪ ↓ Glucose uptake in tissues such as skeletal muscle and fat. ▪ ↑ Glucose production by the liver. 3. Promotion of linear growth; 1. Stimulates proliferation of the cartilage (chondrocytes) at the growth plates (epiphyses) of the long bones, followed by conversion of this cartilage to bone. 2. By late adolescence, ↓epiphyseal cartilage → shafts fused with epiphyses (epiphyseal closure → GH stimulates osteoblast → bones does not elongate, instead, they thickened. 4. Stimulates secretion of insulin-like growth factor-1  Somatomedins GH stimulates cartilage and bone growth indirectly through intermediate substances, produced by the liver under the effect of GH, called somatomedins. Secretion of IGF-I is independent of GH before birth but is stimulated by GH after birth. Their effects on growth are similar to the effects of insulin on growth. Therefore, they are also called insulin-like growth factors (IGFs) They mediates growth of bone and soft tissues via a tyrosine kinase receptor that is structurally homologous with the insulin receptor The most important somatomedins is somatomedin C (also called insulin-like growth factor-1 (IGF-I). It reflects plasma GH levels. Congenital inability to synthesize significant amounts of somatomedin C result in dwarfism like.  Regulation of growth hormone (GH) secretion Factors stimulate secretion: Factors inhibits secretion: 1. Starvation, fasting, hypoglycemia, protein 1. Hyperglycemia, ↑ fatty acids, obesity. deficiency & ↓ fatty acids 2. Aging 2. Stress, exercise & trauma 3. Other hormones 3. Deep sleep a) Exogenous GH 4. Other hormones b) Growth hormone–inhibiting hormone a) Testosterone, estrogen (somatostatin) b) Growth hormone–releasing hormone c) Somatomedins (insulin-like growth factors) c) Ghrelin, secreted by the stomach before meals. ❑GH secretion: Pulsatile, usually undetectable in the serum, apart from 5 to 6 pulses/24h; commonly at night. Its secretion is reflected by plasma level of somatomedin C (IGF-I). Highest during puberty and decreases in adult life.  Disorders of GH – Hypersecretion of GH 1. Gigantism Excess growth of the body → the subjects look like the giants Due to hypersecretion of GH (e.g. pituitary adenomas) in the pre-adult life before the fusion of epiphysis of bone with the shaft. 2. Acromegaly Enlargement, thickening and broadening of bones, particularly in the extremities of the body & facial bones. Due to hypersecretion of GH in adults after the fusion of epiphysis. Could be associated with abnormal growth of internal organs 20–40% of patients with acromegaly have ↑ prolactin → lactation. About 25% of patients have abnormal glucose tolerance tests. Treatment: Somatostatin analogues that inhibit the secretion of GH. Surgical removal of the pituitary tumor. Gigantism Acromegaly  Dwarfism Deficiency of the following hormones (before puberty) may cause growth retardation and dwarfism: 1) Growth hormone or GHRH. 2) Somatomedins (insulin-like growth factor) 3) Thyroid hormones (cretinism) 4) Insulin. Laron dwarfism; characterized by: a) Mutation of GH receptors; resistant (unresponsive) to GH b) Lack of IGF-1 ➔ ↑GH level (or normal) + ↓ IGF-1 Prolactin - PRL Polypeptide; secreted from anterior pituitary. Can be secreted as well from placenta and endometrium 1 Pulsatile secretion around 14 pulses/24h, with a nocturnal peak during sleep. Effect of prolactin 1) Promotes growth of mammary alveoli. 2) Production of milk; causes the alveolar cells to synthesize milk. 3) Inhibition of gonadotrophins (FSH & LH). Results in loss of menstrual cycle during lactation. ❖ Function of prolactin in males is unknown, but excess prolactin causes erectile dysfunction. Prolactin – Regulation of Secretion +ve regulation: the following factors increase PRL secretion: 1. TRH (hypothyroidism may be associated with hyperprolactinaemia) 2. Estrogen. 3. Throughout pregnancy; falls to baseline after delivery. During pregnancy Estrogen & progesterone suppresses its lactogenic effect 4. Stimulation of the nipples associated with suckling Each time the mother nurses her baby, nervous signals from the nipples to the hypothalamus cause a 10- to 20-fold surge in prolactin secretion. 5. During sleep -ve regulation; dopamine (prolactin-inhibiting hormone) (PRL) excess 1. Galactorrhea (milk production) 2. Infertility in both males & females due to inhibition of gonadotropins & disturbed gonadal function (↑PRL → ↓ GnRH → ↓ LH & FSH). A. In female presents with: 1) Menstrual disturbance; amenorrhea, oligomenorrhoea 2) Infertility 3) Reduced libido. B. In male presents with: 1) Loss of libido and/ or erectile dysfunction. 2) Infertility and oligospermia. 3) Gynecomastia (unusual).  Other Anterior Pituitary Hormones Anterior Pituitary H. Functions 1. Stimulates production of thyroid hormones TSH 2. Maintains the size of the thyroid follicular cells 1. Stimulates development of ovarian follicles; FSH 2. Regulates spermatogenesis in the testis 1. Causes ovulation and formation of ovarian corpus luteum. LH 2. Stimulates production of estrogen & progesterone by the ovary 3. Stimulates testosterone production by the testis 1. Stimulates production of adrenal cortex hormones. 2. Maintains the size of adrenocortical zona fasciculata & reticularis. ACTH 3. Effect similar to Melanocyte-stimulating hormones (MSHs) → increase synthesis of the black pigment melanin, 20 Posterior Pituitary  Posterior Pituitary Represents nerve terminals of magnocellular neurons whose cells bodies located in the supraoptic and paraventricular nuclei of hypothalamus. They contain secretary granules (called Herring bodies)1 of neurohypophysial hormones: 1. Antidiuretic hormone (ADH) Synthesized in the supraoptic nuclei of the hypothalamus. 2. Oxytocin Synthesized in the paraventricular nuclei of the hypothalamus ADH & oxytocin are synthesized in hypothalamus, stored & secreted by the posterior pituitary gland.  Posterior Pituitary - Oxytocin Actions of oxytocin 1. Contracts the uterus during labor Descent of the fetus through the birth canal stimulates receptors on the cervix, which send signals to the hypothalamic nuclei and cause secretion of oxytocin. The sensitivity of this response is enhanced by estrogen & inhibited by progesterone. 2. Ejection of milk during lactation Causes contraction of the myoepithelial cells of the mammary glands Secretion is stimulated by breastfeeding infant during suckling Initiated by receptors on the nipples of the breast. 3. Contraction of non-pregnant uterus Facilitate passage of sperm up to the fallopian tube for fertilization. 4. Role of oxytocin in male Causes contraction of the smooth muscle of the vas deferens during ejaculation, propelling sperm toward the urethra. Anti-Diuretic Hormone (ADH) Arginine Vasopressin (AVP) Action: 1. Retention of water, result in: a) ↑ plasma volume, ↓ plasma osmolality. b) Concentrated (hyperosmolar) low volume urine. 2. Vasoconstriction; mediated by GPCR V1 receptors with activation of Ca+2 & phospholipase C 2nd messengers. Mechanism: ADH ↑ H2O permeability of the renal distal tubules and collecting duct ADH binds to GPCR V2 receptors which activates cAMP second messenger system to stimulate the movement of water channels, water exit the cells through: a) Aquaporin-2 (AQP-2), to the luminal membranes. b) AQP-3 and AQP-4, in the basolateral membrane. Regulation of ADH secretion ADH secretion is regulated by osmoreceptors in the anterior hypothalamus Secretion is increased by 1. Increased plasma osmolality. 2. Hypovolemia (↓ECF), hypotension: Achieved by reflexes initiated from receptors found in; carotid sinus, aortic arch and atria. 3. Drugs, including morphine, nicotine, and barbiturates. Factors that decrease ADH secretion include 1. Hypervolemia. 2. Hypertension. 3. Alcohol.  Abnormalities of ADH secretion 1. Excessive ADH secretion: Syndrome of inappropriate ADH secretion (SIADH). oAssociated with: a) CNS disorders; e.g. head trauma, tumors b) Pulmonary diseases; e.g. TB, pneumonia oFeatures of SIADH: 1. Water retention, edema, ↑BP (blood pressure) & ↓ plasma osmolarity. 2. ↓ in urine volume & ↑ urine osmolarity. 2. Deficiency of ADH secretion (Known as diabetes insipidus (DI) oEither due to hypothalamic (neurogenic) or renal (nephrogenic) problems. oFeatures of DI: 1. Hypovolemia (↓ plasma volume) & ↑ plasma osmolarity. 2. Polyurea (↑ urine volume; up to 23 L/day.). ↓ urine osmolarity Neurogenic vs Nephrogenic Diabetes Insipidus (DI) In both conditions, the ability to concentrate urine is impaired Neurogenic DI (central) → ADH secretion is decreased. Nephrogenic DI → the kidneys do not respond appropriately to ADH although the ADH secretion is Normal (or even high). Hypopituitarism Partial or complete deficiency of anterior and/or posterior pituitary hormones. May be due to pituitary or hypothalamic pathology which interferes with the hypothalamic control of the pituitary. Causes 1) Trauma (including traumatic brain injury). 2) Tumors pituitary/parapituitary, infiltration. 3) Radiotherapy 4) Infarction (apoplexy) o Occurs most commonly in patients with pituitary adenomas o May follow post-partum hemorrhage; Sheehan’s syndrome. 5) Infection—tuberculosis, pituitary abscess. 6) Isolated hypothalamic-releasing hormone defciency, e.g. Kallmann’s syndrome due to GnRH deficiency. Hypopituitarism – Clinical features Depend on the type and degree of the hormonal deficits Commonly it follows a characteristic order: a) Secretion of GH, then gonadotrophins being affected first. GH deficiency occurs early in hypopituitarism and is almost invariable in patients with other anterior pituitary hormone deficiencies. b) Followed by TSH and ACTH secretion at a later stage. c) PRL deficiency is rare, except in Sheehan’s syndrome associated with failure of lactation. d) ADH deficiency is virtually unheard of with pituitary adenomas but may be seen rarely with infiltrative disorders and trauma. References Kim E. Barrett,. Ganong’s Review of Medical Physiology. 26th ed. 2019. McGraw-Hill Education. p291 – John E. Hall. Pocket companion to Guyton and Hall textbook of medical physiology. 13th ed. 2016. Elsevier, p 543 – John E. Hall. Guyton and Hall textbook of medical physiology. 13th ed. 2016. Elsevier. Tarig H. Mirghani. The Core of Medical Physiology. 4th ed.