Regulation of the synthesis of steroidogenic enzymes in adrenal cortical cells by ACTH.

Abstract

The mechanism of steroid hormone regulation of specific gene expression in target cells has provided a major focus of interest for investigators concerned with molecular mechanisms involved in cell regulation. This work has been given renewed impetus by the recent cloning and characterization of several steroid hormone receptors (1-6), the trans-acting elements which, upon binding specific ligands, namely the steroid hormones, interact with specific regions of many eukaryotic genes to alter their expression. In contrast, there has been considerably less interest in the mechanisms of regulation of steroid hormone biosynthesis. Yet this is also a topic of great importance, not only because these reactions provide the ligands that interact with the steroid hormone receptors, but also because the steroidogenic enzymes provide excellent model systems for studying the regulation of gene expression by cAMP-dependent mechanisms and by mechanisms involving protein kinase C and tyrosine kinase activity. A variety of mechanisms appear to regulate steroid hydroxylase gene expression in a given cell, and tissue-specific as well as developmental factors play important roles also. In this review, we focus primarily on the regulation of steroid hydroxylase gene expression by cAMP­ dependent mechanisms and, in particular, the mechanisms of ACTH regula­ tion of the synthesis of the steroidogenic enzymes present in the adrenal cortex.