Expression of the steroidogenic acute regulatory protein mRNA in adrenal tumors and cultured adrenal cells

The steroidogenic acute regulatory protein (StAR) has recently been shown to be a factor necessary for cholesterol transport into adrenal and gonadal mitochondria, which is the regulated, rate-limiting step in steroidogenesis. We show here that StAR mRNA is highly expressed in normal adult adrenals (n=9), adrenocortical adenomas (n=16), adrenal hyperplasias (n=6), adrenocortical carcinomas (n=6) and adrenals adjacent to tumor tissues (n=9). There was a good correlation between the expression of StAR and the cholesterol side-chain cleavage enzyme/ 20,22-desmolase (P450 scc) mRNAs both in normal (r=0.93; P<0.01) and in tumor (r=0.97; P<0.001) tissues. No StAR mRNA was detected in Northern blots of liver, kidney, breast, parathyroid or phaeochromocytoma RNAs. In cultured adrenocortical cells, adrenocorticotropin (ACTH), (Bu)(2)cAMP, and cholera toxin increased StAR and P450 sec mRNA accumulation 6- to 18-fold, dose- and time-dependently. StAR (and P450 scc) mRNA increased relatively slowly in response to ACTH treatment, with the maximal increment at 24 h, while the mRNA of the early response gene c-fos peaked within 2 h. The protein kinase inhibitor H-7 inhibited basal and ACTH-induced StAR mRNA expression. Our results show that StAR mRNA is expressed at high levels in normal human adrenals and adrenocortical neoplasms. It is up-regulated in parallel with P450 sec by ACTH in adult adrenocortical cells, which suggests that ACTH is at least one of the key regulators of adrenal StAR expression.