FUNCTIONS & CONTROL OF ANTERIOR PITUITARY,GROWTH HORMONE. DR.HAROON RASHID.

OBJECTIVES List the hormones secreted by the anterior pituitary gland. Discuss Physiological actions of growth hormone. Outline the role of Somatomedins as mediators of Growth Hormone actions. Describe the mechanisms that regulate GH production & release. Describe the sources,actions of somatostatin & relate it to growth hormone control. Correlate this knowledge to Clinical conditions related to hypo & hyper of Growth Hormone.

Hormones secreted by Anterior Pituitary gland. Growth hormone. Thyroid Stimulating hormone. Aderno Corticotropic hormone. Prolactin. Follicle Stimulating Hormone. Leuteinizing Hormone.

GH(=Somatotropin) Structure: Polypeptide, unbranched with191AA Shows species specificity. hGH & monkey’sGH have similar biological activities in humans.

Genes for Gh Genes for human growth hormone, known as growth hormone 1 (somatotropin) and growth hormone 2, are localized in the q22-24 region of chromosome 17 [4][5] and are closely related to human chorionic somatomammotropin (also known as placental lactogen) genes. GH, human chorionic somatomammotropin, and prolactin belong to a group of homologous hormones with growth-promoting and lactogenic activity.growth hormone 1growth hormone 2 [4][5]human chorionic somatomammotropinplacental lactogenprolactina group of homologous hormones

Synthesis & secretion Somatotrophs of ant.pituitary. Released in pulsatile fashion. GHRH(of Hypothalamus)binds receptors on somatotroph(of ant.pit)then cAMP & Ca mediate the release of GH.

Plasma level & circulation About 2-4ng/ml.(0.2 – 1 mg/day). Released in pulses- 10 – 20 pulses / day. Level varies with age. B=at birth C- Childhood P= puberty A= Adult life O= Old age

Nocturnal sleep burst: 1-2hrs after sleep, accounts for 70% of secretion ( More you sleep more you grow!!). Circulating Gh binds with GH binding protein( is a part of receptor ). Half life = 20 min. Metabolism: Mainly in liver, also by kidneys.

GH Receptor Present on membrane of target cells. Has extracellular, transmembrane and intracellular portion.

Mechanism of action of GH GH Directly By IGF-I Produced by Liver IGF types- IGF-I( = Somatomedin C ) & IGF-II

Mechanism of action of GH

ACTIONS GH On Growth & On Metabolism Skeletal tissue * Carbohydrate (cartilage&bones) * Fat Extraskeletal * Proteins (muscles&visceras) * minerals

Actions. Skeletal tissue: 1.Cartilage: proliferation of chondrocytes, increased thickness of epiphyseal cartilage. 2.Bones: St. of osteoblasts, convert cartilage to bone till epiphyseal plate fuses with shaft of long bones. In adults: increases girth of bones.

Actions. Extraskeletal tissue growth: *St skeletal muscle growth ( not contractile unit ) = bulk without power. * Visceral growth increases.

On metabolism On Carbohydrate: * Hyperglycemic:-increases gluconeogenesis(hepatic ),decresases peripheral utilization of glucose, inhibits glycolysis.

On Fat metabolism Gh Adipose tissue Lipolysis Increased FFA in circulation.This acts as energy source during hypoglycemia, fasting and stress.

On proteins ANABOLIC. Promotes protein deposition in tissues by increased uptake of AA,protein synthesis. Causes + ve nitrogen balance.

On minerals Positive balance of Calcium, phosphates,magnesium. Increased renal reabsorption of calcium,phospates,Na.

Other actions On milk production: Gh has lactogenic action. On erythropoiesis: stimulates erythropoiesis. Increases EP from kidney Stimulates growth of lymphocytes. Stimulates growth of genitelia.

Regulation of GH secretion 1.Hypothalamic control by release of a. GHRH b. GHIH. 2. Negative feedback control by a. Somatomedins b. GH c. GHRH

Regulation of GH secretion

Hypothalamic control by release of GHRH GHRH Factors stimulating GHRH secretion and there by increase secretion of GH: -Hypoglycemia(through glucoreceptors) -Emotion,exercise,physical stress(nervous) -Sleep. -Increased plasmaAA levels. -Ghrelin(gh Releasing Peptide)

Hypothalamic control by release of GHIH GHIH( = Somatostatin) Blocks GHRH stimulation Decreased GH Factors stimulating GHIHsecretion & GH. -Hyperglycemia -Plasma FFA

Applied aspect GH: Increased Secretion:1. GIGANTISM 2.ACROMEGALY GH: Decreased secretion: DWARFISM

GIGANTISM Increased secretion of Gh in children i,.e before closure of epiphysis of long bones. Abnormal height(7-8 feet).=gaint. Large hands & feets. Thick lips.macrogosia. Gynaecomastia Loss of libido. Hyperglycemia- insulin-overactivity of beta cells& degeneration- DM If due to tumors- Head ache, visual defects.

Robert WadlowRobert Wadlow, the tallest man known to have lived (2.72 metres or 8 feet 11 inches) with his father, Harold Wadlow (1.82 metres or 6 feet 0 inches)

ACROMEGALY Increased Gh secretion in adults(after epiphyseal closure) Acromegalic face:Thick lips,macroglosia, thick and broadnose,PROGNATHISM. Acral part enlargment- hands,feets. Excessive growth of internal organs- hepato,spleeno,renomegaly. Poor gonadal function.

Prognathism

Brow ridgeBrow ridge and forehead protrusion forehead protrusion normal & acromegalic hands

Acromegalic face

DWARFISM PITUITARY DWARF: -Decreased Gh secretion at early age. -Shortness of strature. -Normal mental activity. -Sexual maturity- may not be if associated with deficiency of Gonadotropin. Otherwise sexual maturity present.

AFRICAN PYGMIES Short strature due to LACK OF GH RECEPTORS IN TISSUES.

LARON DWARFISM CONGENITAL ABNORMALITY OF GH RECEPTORS.

Housy Animal When pancreatectomy is done it results in Diabetes. If hypophysectomy is done diabetes is brought under control. This shows that GH is a diabetogenic hormone.