Association of selenoprotein P with testosterone production in cultured Leydig cells

Selenoprotein P, a plasma selenoprotein, is thought to act as an antioxidan t in the testis, similar to glutathione peroxidase. mRNA encoding selenopro tein P was selectively expressed by Leydig cells, suggesting participation in testosterone production. On the other hand, testosterone production has been linked to O-2 toxicity in cultured Leydig cells. The authors, therefor e, examined changes in selenoprotein P mRNA expression and testosterone pro duction following stimulation by a stable analog cyclic adenosine 3',5'-mon ophosphate (cAMP) in cultured Leydig cells (MLTC-1 cells) under normal O-2 concentrations. Selenoprotein P mRNA was analyzed by Northern blotting, whi le testosterone concentration in culture medium was measured by radioimmuno assay. When cAMP was added to cultures at 0, 0.01, 0.1, or 1 mM, selenoprot ein P mRNA expression showed dose-dependent stimulation. cAMP was added at 0.1 mM to cultures, and the selenoprotein P mRNA expression and testosteron e concentration were evaluated after incubation times of 2, 5, 9, 15, or 24 h. Selenoprotein P mRNA expression was maximal at 9 h. Testosterone concen tration in the medium also increased, becoming maximal at 15 h. Selenoprote in P induced in Leydig cells following cAMP stimulation may counteract O-2 toxicity from cAMP-mediated increases in testosterone production.