Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSOR

DEPT. OF PHARMACOLOGYSSIMS & RC.

ANTERIOR PITUITARY HORMONES

Regulation of anterior pituitary function

Hormones are chemical substances which are synthesized by specific endogenous glands and secreted internally, directly into the blood stream, to act far away from the site of their production and release on the specific target organs. Ex- TSH

Tropic hormones-- target other endocrine glands to release their own hormones. Ex TRH

1. Hypophysiotropic hormones (Neuro-secretions) into the hypothalamo-hypophyseal portal system—

2. Include TRH, GnRH3. These hormones are clustered in discrete hypothalamic

nuclei4. Hypothalamic hormones travel in portal system from

hypothalamus to anterior pituitary5. Hypothalamic hormones regulate hormones secretion

by anterior pituitary

Hypophysiotropic Hormones

Hypothalamopituitary axis Hypothalamic releasing factors Somatotrophs Lactotrophs Gonadotrophs Luteinizing hormone corticotrophs

Regulation of anterior pituitary function

Primarily by the CNS– All pituitary hormones except PRL would decline in the absence of the hypothalamus

By hormones produced in peripheral target glands Example– inhibin secreted from gonads All anterior pituitary hormones secreted in a diurnal

pattern.

Regulation of anterior pituitary function

Short negetive feed back

Long negetive feed back

1. 3.

2.

hormonal families of the anterior lobe:

Glycoprotein hormone family– TSH, FSH, LH

TSH– to stimulate the secretion of thyroid hormone FSH & LH– important for the function of the testes

and the ovaries FSH– growth of ovarian follicles and formation of

sperm LH (in women)– induce ovulation and the formation

of the corpus luteum; stimulate the ovarian production of estrogen and progesterone

LH (in men)– stimulates the production of Testosterone

Anterior Pituitary or Adenohypophysis

Hypo-secretion:During childhood causes

Dwarfism Hyper-secretion:

During childhood causesGigantism (up to 8 – 9 ft.)

During Adulthood causesAcromegaly:

Enlargement of the small bones of the hand and feetEnlargement of the cranium, nose, and lower jawTongue, liver, and kidneys become enlarged

Control of GH secretion

By both Growth hormone releasing hormone (GHRH; from arcuate nuclei mainly); its gene is expressed in the GI tract and the pancreas

and by somatostatin (Growth hormone release inhibiting hormone) (from preoptic periventricular and paraventricular nuclei); its gene is expressed in GI tract and the pancreas

Ghrelin (a peptide from the Arcuate Nuclei) also increase GH secretion via GHRH

Ghrelin is also synthesized in the stomach and is thought to signal feeding behavior

Growth hormone analogues and GHRIH

SERMORELIN-Synthetic analogue of GnRHSOMATOSTATIN-GHRIHOCTREOTIDE-long acting analogue of somatostatinDose-20-200mg sc TDS-carcinoid syndromeBleeding oesophageal varicesTreatment of AIDS associated diarrhoeaInsulinomasSANDOSTATIN-slow release formulation

ADR-steatorrrhoea, gall stones

LANREOTIDE

GHRIH -thyroid tumours Acromegaly

PEGVISOMANT-sc New GH-receptor antagonist-acromegaly Suppress IGF-1 levels -allows dimerisation and blocks the ongoing

conformational changes Demerit- formation of antibodies

Pharmacological actions

Protein synthesis Anabolic effects Somatomedins –IGF1, IGF2 Metabolic consequence insulin like effect

antagonistic to ILEeffect antagonistic to insulin IGF1-released from liverpositive feedback on

hypothalamusGHRIH Increase-GH- sleep, exercise Decrease-L-dopa

Somatotropin

-t1/2-25 minSc-0.2mg/kgAIDSBurn injuriesAnt agingADR-insulin resistanceArthralgia

MECASERMIN

Recombinant human IGF1+ recombinant human IGFBP-3

Maintain desired t1/2 of IGF -short statured children Dose-0.04-0.08 mg/kg ADR-hypoglycemia

Gonadotropins

GnRH-LHFSH-inhibin, activinFSH in females, LH in females

Feed backGonadorelin- synthetic

GnRH agonists

Leuprolide Nafarelin Buserelin Dosrelin Goserelin Triptorelin

GnRH antagonist

Cetrorelix Ganirelix AbarelixDegarelixUses -advanced prostate caUterine fibroids and endometriosisIVF

Natural gonadotropins

From post menopausal womenMenotropinUrofollitropinRecombinant FSHHCGUSES

-infertilityCryptorchismIVFKaposi sarcomaDiagnostic use

Adrenocorticotropin family ACTH (adrenal corticotropic hormone) regulates

hormone secretion by the cortex of the adrenal glands.

ACTH- stimulates –Glucocorticoids, mineralocorticoid and androgens

ACTH-stimulated by trauma and stress

Melanocytes and keratinocytes pigmentation by MSH

(Melanotrope in arcuate neurons)– food intake

Adrenocorticotropin family

Hypo-secretionAddison’s disease –

Simmond’s disease, hypo pituitary cachexia

Hyper-secretion:Cushing’s Syndromemobilization of fat from lower body to the thoracic and upper abdominal regions giving raise to “Buffalo Torso”

COSYNTROPIN

Is a synthetic human ACTH Diagnosis of pituitary adrenal axis ADR- similar to corticosteroids Allergic reactions

Prolactin

Peptide hormone PRIH-PRL release inhibitory hormone-D2 Stimulus for prolactin-suckling mammotropic and lactogenic

Hyperprolactinemia-galactorrhoea, amenorrhea , infertility

Treatment of hyperprolactinemia

Bromocriptine -2.5mg orally-15days Cabergoline-0.25mg orally -BD Pergolide- Quinagolide-0.2-0.6mg/day

OT (oxytocin) and ADH produced in hypothalamus transported by hypothalamo-hypophyseal tract to

posterior lobe (stores/releases hormones)

Posterior Pituitary Hormones