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Testosterone induction of prostaglandin-endoperoxide synthase 2 expression and prostaglandin F₂ production in hamster Leydig cells

¹ Laboratorio de Esteroides, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Vuelta de Obligado 2490, Buenos Aires 1428, Argentina² Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires 1121, Argentina³ Institut für Zellbiologie, Universität München, München D-80802, Germany⁴ Instituto Multidisciplinario de Biología Celular, La Plata 1900, Argentina

Correspondence should be addressed to M B Frungieri at Laboratorio de Esteroides, Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2490, Buenos Aires 1428, Argentina; Email: mfrung{at}dna.uba.ar

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 PGF₂ 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/PGF₂. In active hamster Leydig cells, LH/hCG and testosterone induced PTGS2 and PGF₂ 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/PGF₂ in hamster Leydig cells via androgen receptors and a non-classical mechanism that involves MAPK3/1 activation. Since PGF₂ 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.