Testosterone Induction of prostaglandin-endoperoxide synthase 2 Expression and Prostaglandin F2Ą Production in Hamster Leydig Cells

MATZKIN ME; GONZALEZ-CALVAR SI; MAYERHOFER A; CALANDRA RS; FRUNGIERI MB

REPRODUCTION

BioScientifica

Lugar: Bristol, Reino Unido; Año: 2009 vol. 138 p. 163 - 175

1470-1626

We have previously observed expression of cyclooxygenase 2 (COX2), the key enzyme in the biosynthesis of prostaglandins (PGs), in reproductively active Syrian hamster Leydig cells, and reported an inhibitory role of PGF2a on hamster testicular steroidogenesis. In this study, we further investigated COX2 expression in hamster Leydig cells during sexual development and photoperiodic gonadal regression. Since COX2 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 COX2/PGF2a. In active hamster Leydig cells, LH and testosterone  induced COX2 and PGF2a production, and their actions were abolished by the antiandrogen bicalutamide (Bi). These results indicate that LH does not exert a direct effect on PGs synthesis. Testosterone also stimulated phosphorylation of the extracellular signal-regulated kinase isoforms 1/2 (erk 1/2) within min and h, but the testosterone metabolite dihydrotestosterone (DHT) had no effect on COX2 and erk 1/2. Because Bi and U0126, an inhibitor of the mitogen-activated protein kinase kinase 1 and 2 (MEK1/2) abolished testosterone actions on erk 1/2 and COX2, our studies suggest that testosterone directly induces COX2/PGF2a in hamster Leydig cells via androgen receptors and a non-classical mechanism that involves erk 1/2 activation. Since PGF2a 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.