Growth hormone

GH regulatory pathway

Hypothalamus released GHRH (stimulates GH release) and GHIH (inhibits GH release)

These act on the adenohypophysis with secretes GH

GH acts on target tissues

GH overview

GH is a protein hormone, and acts on membrane receptors

Main targets include liver, muscles, bones and adipose tissue

Circulates blood bound to GH binding protein

Non tropic hormone → acts directly on tissues

Synthesis and regulation

Synthesied by somatotropic cells in anterior pituitary

Release stimulated by GHRH (produced in hypothalamus) → somatocrinin

Release inhibited by GHIH (from hypothalamus) → somatostatin

Indirect actions of GH

Growth promoting

On bones → lengthening (chondrocyte proliferation) and thickening of bones

On muscles → muscle hypertrophy (reduce protein breakdown, increase protein synthesis and amino acid uptakes)

On organs → stim growth of visceral organs and tissue regeneration

Direct actions of GH

Metabolic

Increase blood glucose → less glucose uptake by muscles and fat

Lipolysis → mobilise fatty acids from adipose tissue, provide energy during fasting

Protein syntheis → increase amino uptake, less protein breakdown

Somatomedins

Group of peptide homrones produced in response to GH

They are better known as Insulin-like Growth Factors because of their structural similarity to insulin

GH stimulates liver to produce IGF1 which then acts on tissues

Types include IGF-1 and IGF-2

IGF-1

Primary mediator of GH growth promoting effects

Produced mainly by liver, circulation bound to IGF binding proteins

Stimulation → GH, insulin, thyroid hormones, adequate nutrition

Inhibition → malnutrition, insulin deficiency, chronic illness…

IGF-1 actions

Bone - chondrocyte profileration and osteoblast activity

Muscle - increase amino uptake and protein synthesis

Organs - cell profileration and organ enlargment

Cell cycle - promotes cell division, G1 to S phase

Apoptosis - support tissue survival and regeneration

Stimulators of GH secretion

Low blood glucose - triggers GHRH

High amino acids - signal protein uptake, protein synthesis → fat for energy

Stress/exercise/sleep - increase GHRH

Puberty - enhance GH release and increase liver IGF

Neurotransmitters - serotonin and alpha adrenergic stimulare GHRH

Hormones - TRH, thyroid hormones, androgens, glucocorticoids

Inhibitors of GH secretion

High glucose - increases somatostatin

IGF 1 - negative feedback, increase hypothalamic GHIH

Glucocorticoids - high cortisol supresses GH synthesis

Excess estrogen

GH deficiency

In children → leads to dwarfism

May result from pituitary dysfunction, hypothalamic diseases and endocrine disorders

GH excess

Before puberty → leads to gigantism

After puberty → acromegaly (bones thicken and don’t lengthen)

Can also lead to insulin resistance → diabetes mellitus