Antisteroidogenic actions of hydrogen peroxide on rat leydig cells

Abstract

It has been well known that reactive oxygen species (ROS) are produced in the steroidogenic pathway and spermatozoa. H2O2, one of ROS produced by spermatozoa, appears to be a primary toxic agent. In the present study, we examined the effects of H2O2 on the basal and evoked-testosterone release from primary Leydig cells, the protein expressions of cytochrome P450 side chain cleavage enzyme (P450scc) and steroidogenic acute regulatory (StAR) protein were also investigated. Our preparation was found to contain approximately 87% Leydig cells and very few macrophages. The results demonstrated that H2O2 (>1 x 10(-4) M) significantly inhibited the basal and hCG-stimulated testosterone release. H2O2 abolished forskolin- or 8-Br-cAMP-evoked testosterone release. In the presence of pregnenolone, progesterone, or androstenedione, the inhibitory effect of H2O2 on testosterone release was prevented. H2O2 also inhibited pregnenolone production in the presence of trilostane (an inhibitor of 3beta-hydroxysteroid dehydrogenase), therefore diminished the activity of P450scc in Leydig cells. In addition to the inhibition of hormone secretion, H2O2 also regulated steroidogenesis by diminishing protein expression of StAR. These results suggest that H2O2 acts directly on rat Leydig cells to diminish testosterone production by inhibiting P450scc activity and StAR protein expression.

Effects of polychlorinated biphenyl (Aroclor 1254) on steroidogenesis and antioxidant system in cultured adult rat Leydig cells

“…In view of these findings, it is proposed that an increase in free radical formation results in the inhibition of steroidogenic enzymes and antioxidant defense system during exposure to PCB (Murugesan et al 2005b,c). Hydrogen peroxide can also act directly on rat Leydig cells to decrease the basal and hCG-stimulated testosterone production by inhibiting StAR protein expression and P 450 scc activity (Tsai et al 2003). In the present study, decreased basal and LH-stimulated testosterone production was accompanied by an elevated level of hydrogen peroxide in PCB-exposed Leydig cells.…”

H2O2 at physiological concentrations modulates Leydig cell function inducing oxidative stress and apoptosis

“…Ambiguities exist on the effect of H 2 O 2 versus concentration and duration in different cell populations in vitro. Tsai et al 30 used 400 µM of H 2 O 2 without much effect on the survival of the Leydig cells in vitro. In the study of caspase-dependent and independent events of apoptosis in MCF-7 breast carcinoma cells, H 2 O 2 in the range of 250 µM to 1000 µM were also used.…”

Induction of CYP2E1 in testes of isoniazid-treated rats as possible cause of testicular disorders

“…It is known that CYP2E1 is an effective generator of hydrogen peroxide (Cederbaum, 2006). H 2 O 2 acts directly on rat Leydig cells to diminish testosterone production by inhibiting cytochrome P450 side chain cleavage enzyme (P450scc) activity and steroidogenic acute regulatory (StAR) protein expression (Tsai et al, 2003). Moreover, recently it has been reported, that ROS signaling-mediated c-Jun upregulation suppresses the expression of steroidogenic enzyme genes by inhibiting Nur77 transactivation (one of the major transcription factors that regulate the expression of steroidogenic enzyme genes), resulting in the reduction of testicular steroidogenesis (Lee et al, 2009).…”