Curcumin downregulates 8-br-cAMP-induced steroidogenesis in mouse Leydig cells by suppressing the expression of Cyp11a1 and StAR independently of the PKA-CREB pathway.

Although curcumin was widely applied as a functional food for different diseases, it was found to reduce serum testosterone level and fertility in male animals by unknown molecular mechanisms. Here in our study, we investigated the possible mechanisms of curcumin-suppressed testosterone production in Leydig cells. Our enzyme immunoassay results showed that curcumin cell-autonomously suppressed ovine luteinizing hormone-stimulated testosterone production in primary Leydig cells and 8-bromo-cyclic adenosine monophosphate (8-br-cAMP)-induced progesterone production in MA-10 cells. Furthermore, our real-time PCR, Western blot, and 22R-OHC/pregnenolone supplementing experiment data demonstrated that curcumin suppressed 8-br-cAMP-induced steroidogenesis in Leydig cells by inhibiting the expression of StAR and Cyp11a1. Interestingly, our Western blot data showed that although curcumin suppressed PKA activity, it did not alter the 8-br-cAMP-induced phosphorylation of CREB. On the contrary, the real-time PCR results showed that curcumin suppressed 8-br-cAMP-induced expression of Nr5a1 and Fos, which are crucial for cAMP-stimulated StAR and Cyp11a1 expression in Leydig cells. Collectively, our data demonstrated that curcumin may suppress cAMP-induced steroidogenesis in mouse Leydig cells by down-regulating Nr5a1/Fos-controlled StAR and Cyp11a1 expression independently of the PKA-CREB signaling pathway.