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This version published online on June 1, 2006
Endocrinology, doi:10.1210/en.2006-0090
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Submitted on January 23, 2006
Accepted on May 25, 2006

Cyclooxygenase-2 (COX-2) and Prostaglandin F2{alpha} (PGF2{alpha}) in Syrian Hamster Leydig Cells: Inhibitory Role on LH/hCG-Stimulated Testosterone Production

MÓNICA B. FRUNGIERI*, SILVIA I. GONZALEZ-CALVAR, FERNANDA PARBORELL, MARTIN ALBRECHT, ARTUR MAYERHOFER, and RICARDO S. CALANDRA

Instituto de Biología y Medicina Experimental (M.B.F., S.I.G.-C., F.P., R.S.C.), Consejo Nacional de Investigaciones Científicas y Técnicas, 1428 Buenos Aires, Argentina; Anatomical Institute (M.A., A.M.), Ludwig Maximilians University, D-80802 Munich, Germany; Facultad de Medicina (M.B.F., S.I.G.-C.), Universidad de Buenos Aires, 1121 Buenos Aires, Argentina; Instituto Multidisciplinario de Biología Celular (R.S.C.), 1900 La Plata, Argentina

* To whom correspondence should be addressed. E-mail: mfrung{at}dna.uba.ar.

We have previously found that cyclooxygenase-2 (COX-2), key enzyme in the biosynthesis of prostaglandins (PGs), is present in the testicular interstitial cells of infertile men whereas it is absent in human testes with no evident morphological changes or abnormalities. To find an animal model for further investigating COX-2 and its role in testicular steroidogenesis, we screened testes from adult species ranging from mice to monkeys. By using immunohistochemical assays, we only found COX-2 expression in Leydig cells of the reproductively active (peripubertal, pubertal and adult) seasonal breeder Syrian hamster. COX-2 expression in hamster Leydig cells was confirmed by RT-PCR. In contrast, COX-1 expression was not detected in hamster testes. Since COX-2 expression implies PG synthesis, we investigated the effect of various PGs on testosterone production, and found that PGF2{alpha} stood out because it significantly reduced hCG-stimulated testosterone release from isolated hamster Leydig cells in a dose-dependent manner. This mechanism involves a decreased expression of testicular Steroidogenic Acute Regulatory (StAR) and 17{beta}-hydroxysteroid dehydrogenase (17{beta}-HSD). Testicular concentration and content of PGF2{alpha} in reproductively active hamsters as well as production of PGF2{alpha} from isolated hamster Leydig cells were also determined. Moreover, PGF2{alpha} receptors (FP receptors) were localized in Leydig cells of hamsters and testicular biopsies from patients with Sertoli cell only (SCO) and germ arrest (GA) syndromes. Thus, in this study, we described a COX-2-initiated pathway that via PGF2{alpha} production, FP receptors, StAR, and 17{beta}-HSD represents a physiological local inhibitory system of hCG-stimulated testosterone production in the Syrian hamster testes.
Key words: COX-2 • PGF2{alpha} • FP receptors • steroidogenesis • testis • StAR • 17{beta}-HSD




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