Hypothalamic Pituitary Hormones II Professor Salim M Hassan

Hypothalamic & Pituitary Hormones (II) Professor Salim M. Hassan Mutah Faculty of Medicine 1/30/2022 1

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Anterior Pituitary Hormones v 1. Growth H v 2. ACTH v 3. LH v 4. FSH v 5. TSH v 6. Prolactin 1/30/2022 Regulation by GHRH & GHRIH CRH Gn. RH TRH PIH (Dopamine) 6

Disorders of the pituitary gland v Hypopituitarism: ØChildren: Pituitary Dwarfism (Peter Pan children) ØAdults: Infertility & H deficiencies v Hypersecretion: ØAcromegaly & gigantism ØCushing’s disease ØSexual preciosity ØProlactinemia ØTarget organ failures 1/30/2022 GH ACTH Sex H Prolactin Related H 7

Peter Pan children 1/30/2022 8

Acromegaly 1/30/2022 9

Anterior Pituitary Hormones 1/30/2022 10

Growth hormone (Somatropin) v Single polypeptide chain (191 AA) v Synthesized by somatotroph cells v Stimulation of secretion: ØDuring sleep ØHypoglycaemia ØStress, physical exercise, excitement v Inhibition: ØFeedback control 1/30/2022 11

Pharmacodynamics v Anabolic hormone: ØStimulates growth and cell production ØEnhances longitudinal growth ØEnhances growth of skeletal muscles ØAffects metabolism of protein, CHO, lipids v Somatomedins mediate effects of GH: ØInsulin-like growth factors ØFormed in liver and epiphyses ØExamples: IGF-I & IGF-II 1/30/2022 12

Uses of recombinant human GH v Synthetic GH (genetic engineering) v Indicated as replacement therapy in children with hypopituitarism (pituitary dwarfism): ØPeter Pan children: ØGH deficiency ØFailure of growth ØIncreased body fat ØDecreased muscle mass v It is not indicated in adult hypopituitarism 1/30/2022 13

Uses of recombinant human GH v Treatment of short stature in children with: ØTurner syndrome ØCRF ØOther causes of dwarfism v Treatment of wasting in AIDS v Claimed to have anti-aging effects v Abused by athletes to increase muscle mass 1/30/2022 14

Uses of recombinant human GH v Anti-aging therapy!? to: ØDecrease body fat ØIncrease muscle mass & bone density ØIncrease energy ØImprove immune system function 1/30/2022 15

Recombinant human GH v Adverse effects: ØIntracranial hypertension with visual disturbances ØArthralgia (hands & wrist) ØMyalgia 1/30/2022 16

GH disorders q Excess GH produces: v Acromegaly in adults v Gigantism in children ØPhysical body changes (enlargement) ØDiabetes, hypertension, arthritis v GH excess is reduced by: ØBromocriptine (dopamine agonist) ØOctreotide (somatostatin analogue) 1/30/2022 17

Somatostatin v GH release-inhibiting hormone (GHRIH) v Secreted by hypothalamus, pancreas, stomach v Actions: ØInhibition of GH secretion ØOther effects: ØInhibition of secretion of ACTH, insulin, glucagon, gastrin, secretin ØInhibition of platelet aggregation 1/30/2022 18

Octreotide v Synthetic analogue of somatostatin v Longer half-life; useful sc in: ØAcromegaly to reduce GH release ØDiarrhoea due to VIPOMA ØGIT tumour secreting VIP ØCarcinoid syndrome ØExcess serotonin (5 HT) ØDiabetic diarrhoea 1/30/2022 19

Adrenocorticotrophic H (ACTH) v Polypeptide of 39 AA v Secreted by anterior pituitary v Regulated by CRH that is influenced by: ØStress ØHydrocortisone levels 1/30/2022 20

ACTH v Biological activity: ØFirst 24 AA v Immunological activity: ØRemaining 15 AA 1/30/2022 21

ACTH v Combines with specific receptors v Stimulate adrenal cortex to: ØSynthesize & secret CS & androgens v Its effects are of CS & androgens v Prolonged high doses: ØCushing’s syndrome 1/30/2022 22

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Therapeutic uses of ACTH v Diagnosis of hypofunction of adrenal cortex: ØPrimary (Addison’s disease): high ACTH ØSecondary (pituitary-dependent): low ACTH ØTo study ability of the adrenal cortex to secret HC v In the past, it was used to: ØStimulate suppressed adrenal cortex after prolonged use of CS ØAlternative to corticosteroids in children 1/30/2022 25

ACTH v ACTH use is declining: ØUnpredictable response ØEffects wane with time v Adverse effects: like corticosteroids v Causes more: ØHypertension ØHypokalemic alkalosis 1/30/2022 26

Human Gonadotrophic Hormones v FSH (Follicular stimulating H) v LH (Leutinizing H) v HCG (Human chorionic gonadotrophin) 1/30/2022 27

Human Gonadotrophic Hormones v FSH: ØOvulation ØSpermatogenesis v LH: ØOvulation ØTestosterone production v HCG: ØProgesterone production by corpus luteum ØTestosterone production by testes 1/30/2022 28

Menotrophins v Human menopausal gonodotrophins: ØFrom urine of postmenopausal women v Contain FSH & LH v Useful in induction of ovulation in: ØHypopituitarism (hypogonadotrophin hypogonadism) ØIn vitro fertilisation v Useful in oligospermia with hypogonadotrophin hypogonadism 1/30/2022 29

Therapeutic uses of HCG v Induction of ovulation in: ØHypopituitarism ØIn vitro fertilisation to produce superovulation v Cryptorchidism in children v Delayed puberty 1/30/2022 30

Adverse effects of gonadotrophins v Oedema v Mood changes v Sexual precocity v Multiple pregnancies 1/30/2022 31

Gonadotrophins in therapy q Recombinant FSH q Recombinant LH q Recombinant HCG 1/30/2022 32

TSH v Glycoprotein; controlled by: v TSH regulates: v Useful in thyroid function test: v Level increases by anti-thyroid drugs: ØTRH and thyroid H levels ØThyroid gland function ØRelease of thyroid H ØIodide uptake by the gland ØHigh in primary hypothyroidism ØDecrease thyroid H production 1/30/2022 33

Prolactin v Secreted by anterior pituitary v Consists of 198 AA v Similar to GH chemically & structurally v Physiological actions: ØStimulation and maintenance of lactation ØInhibition of gonadotrophins production 1/30/2022 34

Regulation of Prolactin Secretion v Stimulation by: ØBreast suckling ØTrauma (as during venepuncture), stress, exercise ØSleep ØHypoglycaemia v Inhibition: by dopamine (PRIH) 1/30/2022 35

Drugs and Prolactin v Increase release by: ØDopamine antagonists (phenothiazines) ØOral contraceptive pills (OCP) ØAlpha-methyldopa v Decrease release by: ØBromocriptine 1/30/2022 36

Hyperprolactinemia v May be caused by: ØTumours, drugs as OCP v Presents as: ØAmenorrhoea, infertility, galactorrhoea, impotence v Bromocriptine is effective in treatment ØDopamine D 2 agonist ØUseful in Hyperprolactinemia & suppression of lactation after delivery 1/30/2022 37