Testosterone induction of prostaglandin-endoperoxide synthase 2 expression and prostaglandin F2α production in hamster Leydig cells

Abstract

We have previously observed expression of prostaglandin-endoperoxide synthase 2 (PTGS2), the key enzyme in the biosynthesis of prostaglandins (PGs), in reproductively active Syrian hamster Leydig cells, and reported an inhibitory role of PGF 2a on hamster testicular steroidogenesis. In this study, we further investigated PTGS2 expression in hamster Leydig cells during sexual development and photoperiodic gonadal regression. Since PTGS2 is mostly expressed in pubertal and reproductively active adult hamsters with high circulating levels of LH and androgens, we studied the role of these hormones in the regulation/maintenance of testicular PTGS2/PGF 2a . In active hamster Leydig cells, LH/hCG and testosterone induced PTGS2 and PGF 2a production, and their actions were abolished by the antiandrogen bicalutamide (Bi). These results indicate that LH does not exert a direct effect on PG synthesis. Testosterone also stimulated phosphorylation of the mitogen-activated protein kinase isoforms 3/1 (MAPK3/1) within minutes and hours, but the testosterone metabolite dihydrotestosterone had no effect on PTGS2 and MAPK3/1. Because Bi and U0126, an inhibitor of the MAP kinase kinases 1 and 2 (MAP2K1/2), abolished testosterone actions on MAPK3/1 and PTGS2, our studies suggest that testosterone directly induces PTGS2/PGF 2a in hamster Leydig cells via androgen receptors and a non-classical mechanism that involves MAPK3/1 activation. Since PGF 2a inhibits testosterone production, it might imply the existence of a regulatory loop that is setting a brake on steroidogenesis. Thus, the androgen environment might be crucial for the regulation of testicular PG production at least during sexual development and photoperiodic variations in hamsters.

Cyclooxygenase and prostaglandins in somatic cell populations of the testis

“…On the other hand, in adult hamsters exposed to a short-day photoperiod and also in prepubertal hamsters, testicular COX2 is barely detected, coinciding with low serum concentrations of LH, PRL, and androgens (Frungieri et al 2006, Matzkin et al 2009, 2012b. These results suggest that some hormones (LH, PRL, and/or androgens) could be involved in the regulation of testicular COX2 expression and PG production.…”

“…Revisiting the issue of COX2 expression in hamster Leydig cells, this isoenzyme is detected mainly in reproductively active pubertal and adult hamsters with increased circulating concentrations of luteinizing hormone (LH), prolactin (PRL), and androgens (Frungieri et al 2006, Matzkin et al 2009, 2012b. On the other hand, in adult hamsters exposed to a short-day photoperiod and also in prepubertal hamsters, testicular COX2 is barely detected, coinciding with low serum concentrations of LH, PRL, and androgens (Frungieri et al 2006, Matzkin et al 2009, 2012b.…”

“…This LH action is not derived from a direct mechanism but rather from its stimulatory role in testosterone synthesis (Matzkin et al 2009). In fact, testosterone effects in hamster Leydig cells are exerted via androgen receptors (ARs; Matzkin et al 2009).…”

“…This LH action is not derived from a direct mechanism but rather from its stimulatory role in testosterone synthesis (Matzkin et al 2009). In fact, testosterone effects in hamster Leydig cells are exerted via androgen receptors (ARs; Matzkin et al 2009). The classical mechanism of testosterone action involves binding of this steroid to the cytoplasmic AR, translocation of the newly formed complex into the nucleus, its binding to specific DNA regulatory elements, and, finally, gene transcription regulation.…”

Natural Flavonoids in StAR Gene Expression and Testosterone Biosynthesis in Leydig Cell Aging

“…As LH stimulates testosterone biosynthesis, the increase in testosterone may feed back to induce COX2 expression in Leydig cells. A recent study reported that testosterone induced COX2 expression and prostaglandin F2a production in hamster Leydig cells (Matzkin et al, 2009). These effects of testosterone were abolished by the anti-androgen bicalutamide.…”