Dr. Eman El Eter The pituitary Gland: Anterior pituitary hormones. Posterior pituitary hormones
Pituitary glands • Anterior pituitary hormones • GH • Prolactin • Posterior pituitary hormones • ADH • Oxytocine
Growth hormone (Somatotropin)
Growth Hormone (Somatotropin) Structure and Source of Growth Hormone: • GH is a large peptide hormone, with 191 amino acids • GH is produced by somatotroph cells of the anterior pituitary
Transport of GH in the Blood • About 50% of GH is found in the blood bound to a Growth Hormone-Binding Protein (GHBP). • GHBP increases the half-life of GH, but decreases biological activity (bound GH is not biologically available). • The GHBP is identical to the ligand binding domain of the GH receptor, and may be derived from alternative splicing of the GH receptor RNA.
Growth Hormone (GH; Somatotropin) • The major hormone regulating growth in the body. • Actions of Growth Hormone: - increases skeletal growth - increases muscular growth - increases amino acid uptake and protein synthesis by the cells. - increased use of lipids for energy - decrease glucose re-uptake by the cells & increases blood sugar level. - decreased storage of carbohydrates
Growth Growth Hormone actions
Role of Somatomedins in GH Actions – the GH/IGF Axis • The effects of GH on skeletal and muscular growth appear to be due to the activity of somatomedins, or insulin-like growth factors (IGF-1 and IGF-2) – processed in the liver. • GH acts on the liver, and some other tissues, to increase the production of IGFs. • IGFs then enter the circulation and act on target tissues to enhance growth. • They increase protein synthesis in skeletal muscles.
Gi (-) Regulation of GH Expression in Somatotrophs somatostatin GHRH AC Gs cAMP PKA GH synthesis PIT-1 A txn factor in the Pit
Control of GH secretion: 1. The hypothalamus: a. GHRH GH secretion. b. GHIH (somatostatin) GH secretion 2. Hypoglycemia(fasting) GH secretion. (N.B. glucose intake GH secretion). 3. Muscular exercise GH secretion. 4. Intake of protein or amino acids GH secretion (after meals).
Control of GH secretion: 5. During sleep more in children. 6. Stress conditions, e.g. trauma or emotions GH secretion. 7. FFAs GH secretion
hormone level time Regulation of GH Levels • GH is released from the pituitary in a pulsatile manner: • GH levels are low during the day, but increase during sleep. • There is an overall increase in GH levels during puberty.
Abnormalities of GH secretion GH secretion: • Signs & symptoms ‘in childhood’: Gigantism, • all body tissues grow rapidly, including bones. Height as it occurs before epiphyseal fusion of long bones w their shafts. Hyperglycemia (diabetes).
Abnormalities of GH secretion GH secretion: • Signs & symptoms ‘in adults’: Acromegally, person can’t grow taller, soft tissue continue to grow in thickness (skin, tongue, liver, kidney, …)= organomegally - Enlargement of bones of hands & feet. - Enlargement of membranous bones including cranium, nose, forehead bones, supraorbital ridges. - Protrusion of lower jaw (Proganthism). - Hunched back (kyphosis) (enlargement of vertebrae).
GH = pituitary dwarfism • Manifestations: • Short stature. • Proportionate growth • No mental retardation.
Hypopituitarism • It is hypofunction of the pituitary gland. • It results from disease of the pituitary gland itself (destruction of the anterior lobe) or of the hypothalamus. • Panhypopituitarism is total absence of all pituitary secretions and is rare. Postpartum pituitary necrosis is more likely to occur in women with severe blood loss, hypovolemia, and hypotension at the time of delivery. • It can be a complication of radiation therapy. The total destruction of the pituitary gland results in extreme weight loss, emaciation, atrophy of all endocrine glands and organs, hair loss, impotence, amenorrhea, hypometabolism, and hypoglycemia. Coma and death may occur.
Panhypopituitarism/Hypopituitarism Manifestations are due to deficiency of hormones secreted by pituitary gland: • Gonadotropin deficiency: • Women: Amenorrhea, Infertility • Men: Decreased libido, Decreased beard and body hair. • Corticotropin deficiency: • Fatigue, Decreased appetite, Weight loss, Decreased pigmentation, Abnormal response to stress, Hypotension, Hyponatremia, Fever. • Thyroxin deficiency: • Fatigue, Cold intolerance. • Deficiency of ADH: • Polyuria & Polydipsia
Prolactin Prolactin (PRL), known as luteotropin. A Proteinhormone that in humans is best known for its milk production effect. Prolactin is secreted from the pituitary gland in response to mating, estrogen treatment, ovulation, and nursing. Prolactin is secreted in a pulsatile fashion in between these events. Prolactin also plays an essential role in metabolism, regulation of the and immune system.
Functions of prolactin • The major function of prolactin is milk production (synthesis) • release is inhibited by PIH (dopamine) secreted by the hypothalamus. • suckling response inhibits PIH release and stimulates prolactin secretion.
Target cells Oxytocin Prolactin
Hyperprolactenemia Manifestation: Galactorrehea : Milk secretion in non-lactating female. Infertility (in males& females): as it competes with FSH at receptor site : ovaries/testis. Gynecomastia (males) Cause: Prolactenoma Treatment: Medical: bromocreptin Surgical.
The posterior pituitary gland Composed mainly of cells called ‘Pituicytes’, which act as packing & supporting cells. Stores & releases hormones into the close capillaries. These hormones are produced in hypothalamus.
The posterior pituitary gland hormones • Posterior pituitary gland releases 2 hormones: 1. Antidiuretic hormone (ADH), or arginine vasopressin (AVP). 2. Oxytocin • Both hormones are produced in hypothalamic nuclei: - Supraoptic nucleus (ADH + 1/6 oxytocin) - Paraventricular nucleus (Oxytocin + 1/6 ADH)
The posterior pituitary gland hormones … cont. Both hormones are polypeptides, each contains 9 amino acids. • Both are transported slowly along the • ‘hypothalamo-hypophyseal tract’ in combination • with carrier protein called ‘neurophysin’, to the • nerve endings in the posterior pituitary gland where • they are stored.
Actions of ADH • ADH has 2 main effects: 1. water re-absorption (retention) by distal tubules & collecting ducts of the kidneys decrease osmotic pressure of the blood. * This effect is regulated by V2 receptors, through the action of cAMP. 2. Contraction of vascular smooth muscles generalized vasoconstriction. * This effect is regulated by V1 receptors, through the action of IP3/Ca2+.
Control of ADH release 1. in osmotic pressure of the ECF ( in plasma osmolality), as in dehydration which will stimulate osmoreceptors in the hypothalamus ADH. Hyperosmolarity of ECF -ve feedback Receptors in hypothalamus More ADH release Thirst Collecting ducts of kidneys Water intake Reabsorption of water Dilution of ECF
Control of ADH release …cont. 3. arterial blood pressure, due to blood volume ADH. 4. Age: ADH secretion water retention & hyponatremia. 5. Pain, emotional stress & physical trauma ADH secretion. 6. Drugs, e.g. morphine, barbiturates, & nicotine ADH secretion. 7. Alcohol ADH secretion.
Control of ADH Release • Osmotic stimuli: • Osmoreceptor mediated • osmolality ADH secretion • osmolality ADH secretion • Non-osmotic stimuli (Volume effects) • Baroreceptor mediated (vagus nerve) • blood pressure ADH secretion • blood pressure ADH secretion
Functions of oxytocin • Breast-feeding • contracts the myoepithelial cells of the alveoli (classic neuroendocrine reflex): milk let down reflex. • Childbirth (parturition) • in late pregnancy, uterine smooth muscle (myometrium) becomes sensitive to oxytocin due to the synergistic effect of estrogen. During labor stretch of cervix enhances oxytocin release in a positive feedback manner.