Tumor necrosis factor-α inhibits the stimulatory effect of luteinizing hormone and prostaglandin E 2 on progesterone secretion by the bovine corpus luteum

Abstract

Tumor necrosis factor-α (TNF-α) is involved in the tissue remodeling that occurs in the corpus luteum (CL) during its development and regression. This cytokine is also implicated in the regulation of reproduction by its actions on ovarian steroidogenic cells. The aim of this study was to examine the influence of TNF-α on (1) progesterone (P 4) output by the bovine CL and on (2) the responsiveness of the CL to LH or prostaglandin E 2 (PGE 2) in vitro. In experiment 1, CL (days 8 to 10 of the estrous cycle) were perfused by using an in vitro microdialysis system with TNF-α (0.1, 0.5, or 1 μg/mL) alone or with TNF-α (1 μg/mL) followed by LH (1000 ng/mL) or PGE 2 (2 × 10 −5 M). Basal P 4 release ( P < 0.05) was increased by TNF-α (0.5 or 1 μg/mL). Moreover, TNF-α (1 μg/mL) inhibited the stimulatory effect of LH or PGE 2 on P 4 output ( P < 0.05). In experiment 2, 4 h after intrauterine infusion of TNF-α (0.01 μg/mL or 1 μg/mL), CL (days 8 to 10 of the estrous cycle) were collected by colpotomy, cultured, and stimulated with LH (10 ng/mL) or PGE 2 (10 −6 M). Intrauterine infusion of TNF-α at a concentration of 1 μg/mL increased basal P 4 output by CL ( P < 0.05). Moreover, the intrauterine infusion of TNF-α at a concentration of 0.01 μg/mL inhibited the stimulatory effect of LH or PGE 2 on P 4 output ( P < 0.05). These results indicate that TNF-α (1) does not have an effect on the autonomous, pulsatile release of P 4; (2) increases P 4 secretion by bovine CL with increasing doses, and (3) reduces in a dose-dependent manner the responsiveness of CL to luteotropic factors both directly (after infusion to CL) and indirectly (after intrauterine infusion).