Androgens, especially testosterone produced in Leydig cells, play an essential role in development of the male reproductive phenotype and fertility. However, testicular oxidative stress may cause a decline in testosterone production. Many antioxidants have been used as reactive oxygen species (ROS) scavengers to eliminate oxidative stress to protect steroidogenesis. Astaxanthin (AST), a natural extract from algae and plants ubiquitous in the marine environment, has been shown to have antioxidant activity in many previous studies. In this study, we treated primary mouse Leydig cells or MA-10 cells with hydrogen peroxide (H2O2) to cause oxidative stress. Testosterone and progesterone production was suppressed and the expression of the mature (30 kDa) form of StAR protein was down-regulated in MA-10 cells by H2O2 and cAMP co-treatment. However, progesterone production and expression of mature StAR protein were restored in MA-10 cells by a one-hour pretreatment with AST. AST also reduced ROS levels in cells so that they were lower than the levels in untreated controls. These results provide additional evidence of the potential health benefits of AST as a potential food additive to ease oxidative stress.
Our results suggest that kisspeptin10 does not affect steroidogenesis in adult Leydig cells, but its pattern of expression follows the stages of testicular development. Future studies should determine if kisspeptin regulates testicular development during puberty.
Consumption of ponderosa pine needles causes late-term abortions in cattle and is a serious poisonous plant problem in foothill and mountain rangelands. Isocupressic acid (IA) is the component of pine needles responsible for the abortifacient effect, its abortifacient effect may be due to inhibition of steroidogenesis. To investigate the more detail molecular mechanism, we used MA-10 cell, which is wild used to investigate molecular mechanism of steroidogenesis, to characterize the molecular mechanisms underlying the actions of IA in more detail. In this report, we focus on the function of IA on important steroidogenic genes, including steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD). We found that IA does not affect enzyme activities of these genes but inhibits transcription of P450scc and translation of StAR and P450scc through attenuating cAMP-PKA signaling. Thus, steroid productions of cells were suppressed.
Abstract. 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-cAMPinduced phosphorylation of CREB. On the contrary, the real-time PCR results showed that curcumin suppressed 8-br-cAMPinduced 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.
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