CORTICOTROPIN-RELEASING HORMONE STIMULATES THE EXPRESSION OF THE STEROIDOGENIC ACUTE REGULATORY PROTEIN IN MA-10 MOUSE CELLS

We have previously demonstrated that corticotropin-releasing hormone ( CRH) treatment of MA-10 mouse Leydig tumor cells results in a dose-dep endent stimulation of progesterone production. In view of this observa tion we wished to determine the effects of CRH on the synthesis of the steroidogenic acute regulatory (StAR) protein in these cells. StAR is a steroidogenic tissue-specific, hormone-induced, rapidly synthesized protein previously shown to be involved in the acute regulation of st eroidogenesis, probably by promoting the transfer of cholesterol to th e inner mitochondrial membrane and the cytochrome P450 side-chain clea vage enzyme. Treatment of MA-10 cells with the cAMP analogue dibutyryl cAMP (dbcAMP) resulted in a dose-and time-dependent increase in the l evels of StAR protein that reached a maximum at 800 mu M dbcAMP and wi thin a time period of 6 h. Further, treatment of MA-10 cells with CRH also resulted in a dose-dependent increase in the synthesis of the StA R protein with a maximal response observed at 1 mu M. Slightly differe nt from that observed with dbcAMP, the maximal response to 1 mu M CRH was seen at 4 h following stimulation. These results indicate that the observed increase in steroid production in response to CRH in MA-10 L eydig tumor cells is similar to that previously seen with trophic horm one stimulation acting through the cAMP second messenger pathway, and that it occurs as a result of an increase in the synthesis of the StAR protein.