Cyclooxygenase-2 and Prostaglandin F2alpha in Syrian hamster Leydig cell. Inhibitory role of luteinizing hormone/human chorionic gonadotropin-stimulated testosterone production

FRUNGIERI. MONICA B; GONZALEZ-CALVAR, SILVIA I; PARBORELL, FERNANDA; ALBRECHT, MARTIN; MAYERHOFER, ARTUR; CALANDRA, RICARDO S

ENDOCRINOLOGY

The Endocrine Society

Lugar: United states; Año: 2006 vol. 147 p. 4476 - 4485

0013-7227

We have previously found that cyclooxygenase-2 (COX-2), a 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 found COX-2 expression only 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. Because COX-2 expression impliesPGsynthesis,weinvestigated the effect of variousPGs on testosterone production and found that PGF2 á stood out because it significantly reduced human chorionic gonadotropin-stimulated  testosterone release from isolated hamster Leydig cells in a dose-dependent manner. This mechanism involves a decreased expression of testicular steroidogenic  acute regulatory protein and 17_-hydroxysteroid dehydrogenase.  Testicular concentration and content of PGF2_ in reproductively active hamsters as well as production of PGF2 from isolated hamster Leydig cells were also determined. Moreover, PGF2_ receptors were localized in Leydig cells of hamsters and testicular biopsies from patients with Sertoli cell only and germ arrest syndromes. Thus, in this study, we described a COX-2-initiated pathway that via PGF2_production, PGF2_ receptors, steroidogenic acute regulatory protein, and 17_-hydroxysteroid dehydrogenase represents a physiological local inhibitory system of human chorionic gonadotropin- stimulated testosterone production in the Syrian hamster testes.