ACTH

ACTH (Adrenocorticotropic hormone) or corticotropin is a 39-amino acid peptide hormone (MW=4500) secreted by the pituitary to regulate the production of steroid hormones by the adrenal cortex. ACTH secretion from the anterior pituitary is controlled by both a classical negative feedback control mechanism and CNS-stress mediated control system. Various types of stress or pain perceived in higher levels of the brain modulate secretion of the hypothalamic neurosecretory hormone, corticotropin releasing hormone (CRH), a 41-amino acid peptide. CRH stimulates pituitary ACTH secretion. The second peptide that modulates ACTH secretion is vasopressin (AVP). AVP secretion is also stimulated by stress and acts synergistically with CRH to increase ACTH secretion in the pituitary portal circulation. ACTH increases the synthesis and release of all adrenal sterioids, aldosterone, cortisol and adrenal androgens. It is the principal modulator of cortisol, the most important glucocorticoid in man. As the cortisol level in blood increases, release of ACTH is inhibited directly at the pituitary level. Through this same mechanism, decreasing cortisol levels lead to elevated ACTH levels.

Biologically active ACTH results from enzymatic cleavage of a large precursor molecule, pro-opiomelanocortin (POMC). This molecule contains within its structure the amino acid sequences of ACTH, Pro-ACTH, -melanocyte stimulating hormone, lipotropin, as well as endorphin and the enkephalins. Because the reaction in immunoassays is determined by antigenic structure, not biological function, the usual ACTH RIA reacts with POMC, Pro-ACTH, ACTH and some fragments of the ACTH.