Association of selenoprotein P with testosterone production in cultured Leydig cells

Selenoprotein P, a plasma selenoprotein, is thought to act as an antioxidant in the testis, similar to glutathione peroxidase. mRNA encoding selenoprotein P was selectively expressed by Leydig cells, suggesting participation in testosterone production. On the other hand, testosterone production has been linked to O2 toxicity in cultured Leydig cells. The authors, therefore, examined changes in selenoprotein P mRNA expression and testosterone production following stimulation by a stable analog cyclic adenosine 3',5'-monophosphate (cAMP) in cultured Leydig cells (MLTC-1 cells) under normal O2 concentrations. Selenoprotein P mRNA was analyzed by Northern blotting, while testosterone concentration in culture medium was measured by radioimmunoassay. When cAMP was added to cultures at 0, 0.01, 0.1, or 1 mM, selenoprotein P mRNA expression showed dose-dependent stimulation. cAMP was added at 0.1 mM to cultures, and the selenoprotein P mRNA expression and testosterone concentration were evaluated after incubation times of 2, 5, 9, 15, or 24 h. Selenoprotein P mRNA expression was maximal at 9 h. Testosterone concentration in the medium also increased, becoming maximal at 15 h. Selenoprotein P induced in Leydig cells following cAMP stimulation may counteract O2 toxicity from cAMP-mediated increases in testosterone production.