This chapter discusses the mechanism of action of adrenocorticotropic hormone (ACTH) in the adrenal cortex. ACTH is a 39-amino-acid peptide synthesized and secreted by the corticotrope cells of the anterior lobe of the pituitary gland. ACTH acts on several target tissues, including the adrenal cortex, the adipose tissue, and the brain. ACTH stimulates the synthesis of steroids by the cells of the adrenal cortex. The steroidogenic action of ACTH is mediated primarily by the intracellular messenger cyclic AMP (cAMP) acting via cAMP-dependent protein kinase. Much lower concentrations of ACTH are required for full stimulation of steroidogenesis than for full stimulation of cAMP accumulation in adrenocortical cells. ACTH-stimulated steroidogenesis generally parallels the extent of activation of cAMP-dependent protein kinase. ACTH interacts with a 225 kDA protein in the adrenocortical plasma membrane which is thought to be the ACTH receptor on the basis of (1) binding to antibodies raised against a peptide encoded by a nucleic-acid sequence complementary to that encoding ACTH, and (2) crosslinking of ACTH with a photoactivatable bifunctional reagent.
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