Functional anatomy of pituitary

gland

&

physiology of growth hormone

By: SHANKAR YADAV

MSc. Medical Physiology

Prachand Man Singh Rajbhandari

MSc. Medical Biochemistry

Vikram Shrestha

MSc. Medical Biochemistry

JAWAHARLAL NEHRU MEDICAL COLLEGE

Contents

• Introduction

• History

• Gross anatomy & development

• Histology

• Pituitary hormone

• Growth hormone

• Recent advances

Introduction

• Hypothalamic pituitary unit forms unique component

of endocrine gland

• Controls many aspects of human physiology

• From delivery & feeding of baby to growth &

development to adulthood

• Then to make individual capable of producing

progeny

• Controls various metabolism, water homeostasis,

thyroid & gonad functions

History

• In 150 AD, Galen –first to describe pituitary

• In early 18th century, De Haen described amenorrhea

in pituitary tumor patient

• In 1742 Joseph Lieutaud, demonstrated

hypothalamohypophyseal axis

• In 1772 Saucerotte first to describe Acromegaly

• In 1794 Frank, distinguished diabetes insipidus from

diabetes mellitus

• In 1838 Rathke described formation of gland

Contd….

• In 1887 Minkowiski, linked pituitary gland to number

of symptoms

• In 1892 Vassle Sacchi, showed that removal of pituitary

affect water & mineral metabolism

• In 1907 Schloffer, operate pituitary via nasal route

• In 1909 Aschner, demonstrated hypophysectomy in

growing animal cause Dwarfism

• In 1910 Cushing & team, linked between pituitary &

reproduction

Pituitary gland

Histology

Pituitary Hormones

Growth Hormone

Structure

Synthesis

• GH part of hypophyseal-pituitary axis.

• Synthesized in somatotroph cells

• Response to binding of GHRH to its receptor

• Activating gene transcription by cyclic adenosine

monophosphate-dependent mechanisms

Factors affecting synthesis

Factors influence secretion:

• peptide hormones GHRH Ghrelin

• sex hormone

• Choline and L-DOPA by stimulating GHRH

• Hypoglycemia, arginin by inhibiting somatostatin

release

• Deep sleep

• Niacin as nicotinic acid (Vitamin B3)

• Vigorous exercise

Factors inhibiting

• GHIH – paraventricular nucleus

• Circulating concentrations of GH & IGF

negative feedback mechanism

• Hyperglycemia

• Glucocorticoids

• Dihydrotesterone

Release

• Central and peripheral mechanisms.

• Centrally, its synthesis and release are promoted by

GHRH and inhibited by somatostatin

• Stress, exercise, malnutrition, and anorexia also

stimulate its secretion during the day.

• The release is counter-regulated by three negative-

feedback loops.

Circulation, half life & metabolism

Plasma level :

2-4 ng/mL

Half life :

0-20 minutes

Metabolic clearance rate:

350 L/day

Somatomedin

IGF-I (somatomedin -c) IGF-II (MSA)

secretion Independent of GH before birth

GH stimulates after birth

Independent of GH

Secretions are constant throughout

postnatal growth

Plasma level 10-170 ng/mL 300-800 ng/mL

Receptor Similar to insulin receptor Mannose-6-phosphate receptor

functions Growth stimulating activity

Control skeletal & cartilage growth

Growth during fetal development

Regulation of secretion

Mechanism of action

Actions

types

Direct IGFs mediated

Effect on growth IGF-I

Effect on metabolism IGF-II

Actions

Action contd…

On bone:

• GH promotes linear growth by acting on bone

cartilage & connective tissue

• GH stimulates osteoblast & osteoblast

• GH on growth mediated by somatomedins

Action contd…

Effects on mineral metabolism:

• Promotes bone mineralization on growing children

• Mediated by IGF-1, cause +ve nitrogen balance

• Ca2+ , Po4 , Na+

• Promotes retention of Na+, Cl- & K+

Applied aspects

Hyper secretion of GH

• Tumors of acidophilic cell – somatotrophs

• Depending upon age

1. Gigantism

2. Acromegaly

3. Mixed (acromegalic gigantism)

Gigantism

• Abnormal stature

• Large hand & feet

• Thick lips

• Bilateral

gynaecomastia

• Loss of libido

• Hyperglycemia

Acromegaly

Applied aspects cntd…

Hyposecretion

• Dwarfism:

1. Hypothalamic

2. Pituitary

3. Thyroid

4. ↓sed. liver IGF

Recent advances

• A recent study confirms unliganded GHR are in

dimerised state

• Cultured human fibroblast can produce IGF-I

• GH acts on some target to induce Somatomedin-c,

production which in turn acts locally at the site of

production

References

• Text book of medical physiology

Indu Khurana, section -8 chapter 2, page no. 688-703

• Text book of medical physiology, 2nd edition

by G.K. & Pravati Pal,. Section-VI chapter 44 page

no. 323-339

• Text book of physiology, 5th edition by A.K. Jain

Volume -II, unit- IX page no. 683