Cyclooxygenase 2 (COX2) / 15d-PGJ2 system in hamster Sertoli cells: its modulation by FSH/testosterone and its involvement on glucose uptake

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

Houston

Congreso; 94th Annual Meeting. The Endocrine Society.; 2012

The Endocrine Society.

  We have previously described a stimulatory effect of testosterone (T) on cyclooxygenase 2 (COX2) expression and prostaglandin (PGs) synthesis in Syrian hamster Leydig cells (1), as well as the involvement of PGs in the modulation of T production (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 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 cultivated under basal conditions for 48h. We detected expression of COX2 (by Western blot), production of certain PGs (PGD2, PGF2a, 15d-PGJ2 by immunoassay) and the presence of PGs receptors (DP, FP, PPARg by RT-PCR) in hamster SC. The subsequent incubation of SC in the presence of FSH (100 ng/ml), T (1 µM) or the plasma membrane-impermeable T-BSA (1 µM) for 1h significantly induced the expression of COX2 and the phosphorylation of MAPK1/2 evaluated by Western blot, and the production of 15d-PGJ2 quantified by immunoassay. The stimulatory effect of FSH and T-BSA on COX2 expression was abolished in the presence of the selective MEK1/2 inhibitor, U0126. In addition, T-BSA-induced COX2 expression and MAPK1/2 phosphorylation were reverted by the antiandrogen bicalutamide. Glucose uptake was also determined by a radioactive assay. 15d-PGJ2 (1 µM) decreased the uptake of this monosaccharide, an effect abolished by the PPARg antagonist, BADGE. FSH, T and T-BSA induced glucose uptake and this effect was 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/ PPARg. These results demonstrate the presence of a COX2/PGs system in hamster SC and its up-regulation by FSH and T. Furthermore, results obtanined in the presence of the plasma membrane-impermeable T-BSA suggest that T exerts a stimulatory effect on COX2/PGs via androgen receptors and a non-classical mechanism that involves MAPK1/2 activation. Overall, the COX2/15d-PGJ2 system might act as a local modulator of the FSH/T action on energy balance in hamster SC.   (1) Matzkin et al., Reproduction 138: 163-175, 2009. (2) Frungieri et al., Endocrinology, 147: 4476-4485, 2006.