Cyclooxygenase 2 (COX2)/15d-PGJ2 System in Hamster Sertoli Cells: Its Modulation by FSH/Testosterone and Its Involvement on Glucose Uptake

MATZKIN ME; PELLIZARI EH; CALANDRA RS; CIGORRAGA SB; FRUNGIERI MB

Houston

Congreso; 94th Annual Meeting of the Endocrine Society; 2012

The Endocrine Society

We have previously described a stimulatory effect of testosterone (T) on cyclooxygenase 2 (COX2) expression, prostaglandin (PG) synthesis as well as the involvement of PGs in the modulation of T production in hamster Leydig cells (1, 2). In the present study, we investigated the existence of a COX2/PGs system in hamster Sertoli cells (SC), its regulation by hormones (FSH and T) and the effect of one PG, 15d-PGJ2, on SC glucose uptake.The Syrian hamster is a seasonal breeder. The exposure of adult hamsters to a short photoperiod (6h light/day) for 16 weeks triggers a drastic decrease in plasma levels of LH, FSH and T, as well as a severe testicular regression. SC were purified from testes of regressed adult hamsters and cultured under basal conditions for 48h. Subsequent incubation of SC in the presence of FSH (100 ng/ml), T (1 uM) or the plasma membraneimpermeable T-BSA (1 uM) for 1h significantly induced COX2 expression and MAPK1/2 phosphorylation (determined by Western blot) and 15d-PGJ2 production (quantified by immunoassay). The stimulatory effect of FSH and T-BSA on COX2 expression was abolished by the selective MEK1/2 inhibitor, U0126. In addition, T-BSA-induced COX2 expression and MAPK1/2 phosphorylation were reverted by the antiandrogen bicalutamide.The presence of PPAR , the nuclear receptor for PGJ2 derivatives, was detected in hamster SC by RT-PCR and immunocytochemistry. 15d-PGJ2 (1 uM) decreased the uptake of 3H-2-deoxyglucose (2DOG), a non-metabolizable glucose analogue, into SC. This effect was abolished by the PPAR antagonist, BADGE. On the other hand, FSH, T and T-BSA increased 2DOG uptake, an effect further stimulated in the presence of meloxicam, a selective COX2 inhibitor. Thus, FSH and T regulate glucose uptake in hamster SC through, at least, two mechanisms, a direct positive modulation and an indirect negative effect exerted via 15d-PGJ2/PPAR .In summary, these results demonstrate the presence of a COX2/PGs system in hamster SC and its up-regulation by FSH and T. Furthermore, results obtained in the presence of the plasma membrane impermeable T-BSA suggest that T exerts a stimulatory effect on COX2/PGs through a non-classical mechanism that involves the presence of androgen receptors and  MAPK1/2 activation. Overall, the COX2/15d-PGJ2 system might act as a local modulator of FSH and T actions on hamster SC function.