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Antisteroidogenic actions of hydrogen peroxide on rat leydig cells
Author(s) -
Tsai ShiowChwen,
Lu ChienChen,
Lin ChiuShuang,
Wang Paulus S.
Publication year - 2003
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10738
Subject(s) - cholesterol side chain cleavage enzyme , pregnenolone , steroidogenic acute regulatory protein , leydig cell , medicine , endocrinology , testosterone (patch) , chemistry , forskolin , reactive oxygen species , androstenedione , hormone , cytochrome p450 , biology , steroid , androgen , metabolism , biochemistry , gene expression , luteinizing hormone , stimulation , gene
It has been well known that reactive oxygen species (ROS) are produced in the steroidogenic pathway and spermatozoa. H 2 O 2 , one of ROS produced by spermatozoa, appears to be a primary toxic agent. In the present study, we examined the effects of H 2 O 2 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 H 2 O 2 (>1 × 10 −4 M) significantly inhibited the basal and hCG‐stimulated testosterone release. H 2 O 2 abolished forskolin‐ or 8‐Br‐cAMP‐evoked testosterone release. In the presence of pregnenolone, progesterone, or androstenedione, the inhibitory effect of H 2 O 2 on testosterone release was prevented. H 2 O 2 also inhibited pregnenolone production in the presence of trilostane (an inhibitor of 3β‐hydroxysteroid dehydrogenase), therefore diminished the activity of P450scc in Leydig cells. In addition to the inhibition of hormone secretion, H 2 O 2 also regulated steroidogenesis by diminishing protein expression of StAR. These results suggest that H 2 O 2 acts directly on rat Leydig cells to diminish testosterone production by inhibiting P450scc activity and StAR protein expression. © 2003 Wiley‐Liss, Inc.