It is a 39 amino acid single chain peptide, MW 4500, derived from a larger peptide proopio melanocortin (MW 30,000) which also gives rise to endorphins, two lipotropins and two MSHs.
ADRENOCORTICOTROPIC HORMONE (ACTH,
CORTICOTROPIN)
It
is a 39 amino acid single chain peptide, MW 4500, derived from a larger peptide
proopio melanocortin (MW 30,000) which also gives rise to endorphins, two lipotropins and two
MSHs.
Physiological Function
ACTH
promotes steroidogenesis in adrenal cortex by stimulating cAMP formation in
cortical cells (through specific cell surface G protein coupled receptors) → rapidly increases the
availability of cholesterol for conversion to pregnenolone which is the rate
limiting step in the production of gluco, mineralo and weakly androgenic
steroids. Induction of steroidogenic enzymes occurs after a delay. The stores
of adrenal steroids are very limited and rate of synthesis primarily governs
the rate of release. ACTH also exerts trophic influence on adrenal cortex
(again through cAMP): high doses cause hypertrophy and hyperplasia. Absence of
ACTH results in adrenal atrophy. However, zona glomerulosa is little affected
because angiotensin also exerts trophic influence on this layer and sustains
aldosterone secretion.
Regulation Of Secretion
Hypothalamus
regulates ACTH release from
pituitary through corticotropin releasing hormone (CRH). The CRH receptor on
corticotropes is also a G protein coupled receptor which increases ACTH
synthesis as well as release through increased cAMP. Secretion of ACTH has a
circadian rhythm. Peak plasma levels occur in the early morning, decrease
during day and are lowest at midnight. Corticosteroids exert inhibitory
feedback influence on ACTH production by acting directly on the pituitary as
well as indirectly through hypothalamus.
A
variety of stressful stimuli, e.g. trauma, surgery, severe pain, anxiety, fear,
blood loss, exposure to cold, etc. generate neural impulses which converge on median
eminence to cause elaboration of CRH. The feedback inhibition appears to be
overpowered during stress—rise in ACTH secretion continues despite high plasma
level of cortisol induced by it. Vasopressin has been found to enhance action
of CRH on corticotropes and augment ACTH release.
Pathological Involvement
Excess
production of ACTH from basophil
pituitary tumours is responsible for some cases of Cushing’s syndrome.
Hypocorticism occurs in pituitary insufficiency due to low ACTH production.
Iatrogenic suppression of ACTH secretion and pituitary adrenal axis is the most
common form of abnormality encountered currently due to the use of pharmacological
doses of glucocorticoids in nonendocrine diseases.
Use
ACTH is used primarily
for the diagnosis of disorders of pituitary adrenal
axis. Injected i.v. 25 IU causes increase in plasma cortisol if the adrenals
are functional. Direct assay of plasma ACTH level is now preferred.
For therapeutic
purposes, ACTH does not offer any advantage over corticosteroids and is more
inconvenient, expensive as well as less predictable.
Related Topics
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