adrenocorticotropin (ACTH). Secretion is also under circadian regulation.
Vasopressin and angiotensin II augment this positive response but by themselves
do not initiate it. ACTH is derived from the precursor polypeptide proopiome-
lanocortin after cleavage in the pituitary to release ACTH plus P-lipotropin, an
endorphin precursor with melanocyte-stimulating activity. ACTH binds to
plasma membrane receptors in the adrenal gland to stimulate production
of cortisol, a signaling response mediated by adenylate cyclase (Figure 49-1).
Increased blood cortisol levels exert feedback inhibition of ACTH secretion, a
feedback loop acting at multiple levels including the hypothalamus, the pitu-
itary and the central nervous system. Under separate positive control by norep-
inephrine, the intermediate pituitary converts ACTH to melanocyte-stimulating
hormone (P-MSH) plus CLIP (corticotropin-like intermediary peptide).
Most cases of Addison disease are a result of idiopathic atrophy of
the adrenal cortex induced by autoimmune responses, although a num-
ber of other causes of adrenal cortex destruction have been described.
Hypoadrenocorticism results in decreased production of cortisol and, in some
Figure 49-1. The sequence of events leading to the release of cortisol from the
adrenal gland. Binding of ACTH to cell surface receptors activates adenylate
cyclase to produce cAMP, which in turn activates protein kinase A. This causes
phosphorylation events to occur that cause cholesterol to be released from cho-
lesterol ester droplets in the cell. This initiates the conversion of cholesterol to
cortisol, which is then released into the bloodstream.
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