Steroidogenic acute regulatory protein expression is dependent upon post-translational effects of cAMP-dependent protein kinase A

Tropic hormones acutely; stimulate adrenal acid gonadal steroidogenesis by activation of the cAMP-dependent protein kinase A (PKA) signaling pathway a nd subsequent induction of Steroidogenic Acute Regulatory (StAR) protein (S tAR) expression. We present a comparative study of StAR regulation in mouse adrenocortical Y1 and the derived PKA mutant Kin-X cell lints to evaluate the PKA requirement for StAR expression. A parallel increase in StAR steady -state mRNA and protein was observed in Y1 cells. StAR mRNA was induced in 8-Br-cAMP-treated Kin-8 cells with maximal expression levels approx. 50% of that observed in Y1 cells. However. a corresponding increase in StAR prote in, as detected by Western analysis, was absent in the Kin-8 cells. A simil ar distribution of StAR mRNA in active polysome fractions was observed for both 8-Br-cAMP-treated Y1 and Kin-8 cells, as well as a 2-fold increase in incorporation of [S-35]methionine into StAR, which indicated translation wa s not blocked in Kin-8 cells. Together these data indicate that PKA functio ns at the post-translational level to regulate StAR expression and we propo se that phosphorylation of StAR by PKA contributes to protein stability (C) 2001 Elsevier Science Inland Ltd. All rights reserved.