Anterior pituitary hormones

Dr.U.P.Rathnakar
MD.DIH.PGDHM
1

-ve long feed back

-ve short loop

Growth Hormone[GH]
Secreted by somatotropes
Regulation of secretion [Feed back-IGF-Short and long]] Stimulate release GHRH [L-dopa, damphetamine,Betablockers] Deep sleep,Starvation Exercise/Trauma/Excitement Hypoglycemia
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Inhibit release GHRIH [Adrenergic agonists] [DA-in Acromegaly] [Somatostatin] Hyperglycemia

 Chondrocyte conversion to osteoblasts

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Growth Hormone[GH] Actions

[Indirect action] GHIGF-1[Liver] Tissues Anabolic and growth promoting effect 1. Epiphysis of long bones
2. Insulin like action on IGF-1 receptors[Lipogenesis and glucose uptake-muscles]

[Direct action] Diabetogenic[Lipolysis,Glycogenolysis, glucose uptake]

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Excess/deficiency
Excess
Childhood-Gigantism Adults-Acromegaly

Deficiency
Children-Pituitary dwarf [GH deficiency] [IGF-deficiency-do not respond to GH] Adults-rare

Twelve-year-old boy with pituitary gigantism measuring 6'5"

Acromegaly

GH related Preparations
1. GHRH analogueSERMORELIN 2. Recombinant GH[rhGH]SOMATROPIN & SOMATREM 3. Recombinant IGF-1MECASERMIN 4. GH release inhibitorsSomatostatin analogues- OCTREOTIDE, SANDOSTATIN, LANREOTIDE

Preparations
GHRH analogue- SERMORELIN Recombinant GH[rhGH]SOMATROPIN & SOMATREM Recombinant IGF-1MECASERMIN GH release inhibitors-Somatostatin analogues- OCTREOTIDE, SANDOSTATIN, LANREOTIDE

GHRH analogueSERMORELIN

Diagnostic-To test capacity and function of somatotrophs in children Rarely in GH defeciency

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1. 2. 3. 4. 5.

GHRH analogue- SERMORELIN Human GH-Not used. Why? Recombinant GH[rhGH]- SOMATROPIN & SOMATREM Recombinant IGF-1- MECASERMIN GH release inhibitors-Somatostatin analoguesOCTREOTIDE, SANDOSTATIN, LANREOTIDE

GH
Human and animal derivatives are no longer used-Why?
Creutzfeldt-Jacob disease were found in individuals that had received cadaver-derived HGH Animal source does not match human GH in AA sequence

[Recombinant GH[rhGH]- SOMATROPIN & SOMATREM] Indications 1. Pitutary dwarfs-i.m./s.c/thrice a week up to 25 years 2. Turners syndrome 3. Renal failure in children 4. GH deficiency in adults-once in 2 weeks 5. Anabolic agent-AIDS, Burns, ADEs Type-2 DM, insulin resistance, arthralgia, pain at inj.site, fluid retention, hypopthyroidism, raised ICT

Preparations

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1. 2. 3. 4. 5. 6.

GHRH analogue- SERMORELIN Human GH-Not used. Why? Recombinant GH[rhGH]- SOMATROPIN & SOMATREM Recombinant IGF-1- MECASERMIN GH release inhibitors-Somatostatin analoguesOCTREOTIDE, SANDOSTATIN, LANREOTIDE GH rec.antagonist-Pegvisomant

Recombinant IGF-1- MECASERMIN

For IGF-1 deficiency in children [GH normal] Mutant GH receptor Do not respond to GH

Preparations

12

1. 2. 3. 4. 5. 6.

GHRH analogue- SERMORELIN Human GH-Not used. Why? Recombinant GH[rhGH]- SOMATROPIN & SOMATREM Recombinant IGF-1- MECASERMIN GH release inhibitors-Somatostatin analoguesOCTREOTIDE, SANDOSTATIN, LANREOTIDE GH rec.antagonist-Pegvisomant

Somatostatin & analogues

Somatostatin is of limited use Short half life, not specific for GH, Rebound GH excess Octreotide and Lanreotide- Long acting analogues More potent in inhibiting GH Less action on other secretions[Like insulin] Indications Acromegaly Carcinoid syndrome, VIP secreting tumors, secretory diarrhoea with IBS Esophageal varices & Bleeding peptic ulcer [decreases mucosal blood flow]

Preparations

13

1. 2. 3. 4. 5. 6.

GHRH analogue- SERMORELIN Human GH-Not used. Why? Recombinant GH[rhGH]- SOMATROPIN & SOMATREM Recombinant IGF-1- MECASERMIN GH release inhibitors-Somatostatin analoguesOCTREOTIDE, SANDOSTATIN, LANREOTIDE GH rec.antagonist-Pegvisomant

Somatostatin & analogues

Somatostatin is of limited use Short half life, not specific for GH, Rebound GH excess Octreotide and Lanreotide- Long acting analogues More potent in inhibiting GH Less action on other secretions[Like insulin] Indications Acromegaly Carcinoid syndrome, VIP secreting tumors, secretory diarrhoea with IBS Esophageal varices & Bleeding peptic ulcer[decreases mucosal blood flow]

ADEs
Abdominal pain, gall stones[biliary secretion], steatrrhoea

Sandostatin-Slow release formulation

Preparations

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1. 2. 3. 4. 5. 6.

GHRH analogue- SERMORELIN Human GH-Not used. Why? Recombinant GH[rhGH]- SOMATROPIN & SOMATREM Recombinant IGF-1- MECASERMIN GH release inhibitors-Somatostatin analoguesOCTREOTIDE, SANDOSTATIN, LANREOTIDE GH rec.antagonist-Pegvisomant

Pegvisomant
GH-receptor antagonist Prevents peripheral binding of GH Indication-acromegaly Paradoxical increase in GH-Limited long term use Antibodies-Limited long term use

Preparations

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Prolactin
Lactotrophs-Ant pit Releasing factors not known [TRH stimulates] Suckling PRIH [DA] from hypothalamus
DA agonists[DA, bromocryptine] PRL levels DA antagonists [CPZ, haloperidol, metoclopramide] PRL levels
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Prolactin Actions
Mammotropic & Lactogenic Suppresses GnRH secretion [Lactation amenorrhoea & contraception] Immune mechanism-action on lymphocytes

Excess-[Tumors, drugs, hypothyroidism]

Galactorrhoea-Amennorrhoea-infertility syndrome Men-loss of libido , infertility, gynecomastia PRL not used clinically
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DA agonists[PRL]
Bromocryptine

Ergot derivative DA agonist[D1>D2], adrenergic blocker]

Decrease PRL levels GH. But paradoxically GH levels-pit.tumors Antiparkinsonism-DAergic [levodopa like] Vomiting-action non CTZ Hypotension GI motility

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DA agonists[PRL]

Bromocryptine Indications-Microprolactinomas Acromegaly Parkinsonism Oral ADEs
Nausea, vomiting, constipation, postural hypotension Can be minimized by starting with low dose

Cabergoline- New D2 agonist. Long acting

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GnRH
[Gonadotrpin Releasing Hormone] stimulate release of

Gonadotropins[FSH&LH]

Pulsatile GnRHRelease of FSH or LH Negative feed[by hormones] back[Short & Long loop] Positive feed back-puberty & LH surge

GH-GHRH-Gn Gonadotropins-GnRH20

GnRH
Gonadotrpin releasing hormone
Continuous administration initially stimulates THEN desensitizes the receptors in gonadotropes and loss of Gn release Physiological GnRH-Pulsatile So GnRH is used to inhibit the release of Gn not for treatment of hypogonadism

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GnRH-Gonadorelin
Synthetic GnRH Short acting[half life 4-6 mts] Six months of tt required Uses 1. Diagnostic-Hypothalamus or Pit. Hypogonadism 2. Hypothalamic hypogonadotropic Hypogonadism-males and females[Not very useful]

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GnRH

[Superactive] Long acting agonists Leuprolide, Nafarelin, Buserelin, Deslorelin, Goserelin, Triptorelin, Histrelin i.m., s.c, nasal spray Long acting-1-2 weeks Used to suppress FSH/LH

[Pharmacological oopherectomy /orchidectomy] Uses: Precocious puberty, Polycystic ovarian disease, prostate ca, IVF, Endometriosis, ER sensitive breast cancer

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GnRH Rec. Antagonists

Citrorelix, ganirelix, abarelix, degarelix Competitive GnRH receptor blockers in Ant pit. Uses same GnRH analogues Fast acting

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Gonadotropins[FSH&LH]
Pulsatile GnRHRelease of FSH or LH [Continuous exposure- release] Negative feed[by hormones] back[Short & Long loop] Positive feed back-puberty & LH surge

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Gonadotropins[FSH&LH] Actions
FSH LH

Males

Females

Females
Induction of ovulation Corpus luteum-formation& maintenance

Males
Synthesis of testosterone by Leydig cells

Spermatog- Gametogenesis -enesis by Follicular Sertoli cells development

Estrogen/progesterone production Regulation of menstrual cycle

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Altered physiology of Hypothalomo-pituitary-gonadal axis

Premature activation-Precocious puberty Derangement-Delayed puberty Excess of FSH/LH-Polycystic ovaries Deficiency of FSH/LHamennorrhoea/sterility/oligozoos permia/impotence

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Gonadotropins-Preparations [Administered by i.m.]

1. Menotropins[FSH+LH]-From urine of menopausal women 2. Pure FSH 3. Human chorionic gonadotropin-urine of pregnant women[HCG] 4. Recombinant FSH[rFSH]

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Gonadotropins-Uses [Administered by i.m.]

Amenorrhoea & infertility-to induce ovulation Hypogonadotropic hypogonadism Delayed puberty or oligozoospermia Sterility Cryptorchism In vitro fertilization-to induce multiple ovulation & harvesting ADEs-Polycystic ovary

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Assisted reproduction protocol

Maturation

Recipient

Induce ovulation

Support luteal phase

To prevent endogenous LH surge

30 Katzung pharmacology 12th ed.