The intracellular messenger for ACTH

ACTH (adrenocorticotropic hormone, corticotropin) 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, adipose tissue and brain. It is synthesized as part of proopiomelanocortin (POMC) as amino acids 132-170 of this molecule, which is proteolytically cleaved to produce ACTH [1], 

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 acting via cyclic AMP-dependent protein kinase. The evidence for this is that (i) ACTH stimulates cyclic AMP production in intact adrenocortical cells and in plasma membrane preparations (ii) cyclic AMP analogues added to adrenocortical cells stimulate steroidogenesis to the same extent as ACTH and (iii) mutant adrenocortical cells with defective cyclic AMP-dependent protein kinase lack stimulation of steroidogenesis by ACTH [2], 

Although the primary mode of action of ACTH is via cyclic AMP and cyclic AMP-dependent protein kinase (A-kinase), calcium probably plays a secondary role in enhancing and modulating the action of ACTH via the A-kinase pathway. This is discussed later in the consideration of the interaction of the A-kinase pathway of activation by ACTH and other second messenger systems involving calcium and protein kinase C. 

Unlike some other hormones which act on the adrenal cortex, such as angiotensin II and acetylcholine, ACTH probably does not have a major portion of its action via the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) and the gen- 

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