Type 1 and 2 isoenzymes of cAMP-dependent protein kinase in Leydig cell steroidogenesis

Abstract

This study examined the functional significance of the type 1 (T1) and type 2 (T2) cAMP-dependent protein kinase (PK-A) isoenzymes in androgen production by mouse Leydig cells. Leydig cells were exposed to cAMP analogues selective for either of the two cAMP binding sites on the regulatory subunits of each PK-A isoenzyme. As the two binding sites have been shown to exhibit positive cooperativity, coexposure to the appropriate combination of analogues will synergistically increase androgen production if either T1 or T2 PK-A is present and functional in the cell. We found that both PK-A isoenzymes are present and functionally active, though the T1 kinase predominates. Coexposure to the cAMP analogues and cAMP or luteinizing hormone also synergistically increased androgen production via both isoenzymes while forskolin acted only via the T1 isoenzyme, suggesting that forskolin may instigate cellular events in addition to cAMP synthesis.