EXPRESSION OF THE STEROIDOGENIC ACUTE REGULATORY PROTEIN MESSENGER-RNA IN ADRENAL-TUMORS AND CULTURED ADRENAL-CELLS

The steroidogenic acute regulatory protein (StAR) has recently been sh own to be a factor necessary for cholesterol transport into adrenal an d gonadal mitochondria, which is the regulated, rate-limiting step in steroidogenesis. We show here that StAR mRNA is highly expressed in no rmal adult adrenals (n=9), adrenocortical adenomas (n=16), adrenal hyp erplasias (n=6), adrenocortical carcinomas (n=6) and adrenals adjacent to tumor tissues (n=9). There was a good correlation between the expr ession of StAR and the cholesterol side-chain cleavage enzyme/ 20,22-d esmolase (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 blot s 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- t o 18-fold, dose- and time-dependently. StAR (and P450 scc) mRNA increa sed relatively slowly in response to ACTH treatment, with the maximal increment at 24 h, while the mRNA of the early response gene c-fos pea ked within 2 h. The protein kinase inhibitor H-7 inhibited basal and A CTH-induced StAR mRNA expression. Our results show that StAR mRNA is e xpressed at high levels in normal human adrenals and adrenocortical ne oplasms. 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.