Regulation of luteal function and prolactin secretion in the pig: effects of orally and intracerebroventricularly applied RU 486 and relaxin

Abstract

<p>RU 486, a progesterone receptor antagonist, was used to investigate the effects of interruption of progesterone binding to its receptor on luteal function and gonadotropin secretion of pigs with aging corpora lutea. RU 486 was administered orally to hysterectomized gilts once a day on days 111-115 (estrus = day 0) at two dosages (group 1, 2 mg/kg BW; group 2, 4 mg/kg BW). During 5 days of RU 486 treatment, plasma progesterone concentrations in both treated groups were markedly elevated (32 and 37 ng/ml for groups 1 and 2) compared with 22 ng/ml in the controls (group 3; P < 0.01). Prolactin concentrations increased in both groups (9 and 13 ng/ml) and differed significantly from those of the controls (3 ng/ml) (P < 0.04). Pregnant gilts received RU 486 orally once a day at 0800 hours at 4 mg/kg BW beginning on day 111 until parturition occurred. Parturition was induced on day 112.7 after only two RU 486 treatments compared with day 114.7 in the control group (P < 0.01). Progesterone decreased abruptly (P < 0.01) from a pretreatment mean of 11 to <0.6 ng/ml during the 2 days that RU 486 was given. Results from this study provide strong evidence that the antagonistic effect of RU 486 on progesterone receptor results in an abrupt increase in PRL and progesterone secretion in hysterectomized gilts with aging corpora lutea. In marked contrast with hysterectomized animals, the acute luteolytic effects of RU 486 depend on the presence of the uterus and/or conceptuses in the pig;To test whether relaxin and RU 486 exert their actions directly on CNS/pituitary gland to affect PRL secretion, a second experiment was conducted. Hysterectomized pigs with aging corpora lutea were given acute intracerebroventricular (ICV) infusion of relaxin (300 Units, n = 6) or RU 486(4 mg, n = 5) on days 111, 113, and 115. ICV injections of relaxin and RU 486 markedly stimulated PRL secretion on day 111 (from 8.2 to 38.3 and 9.7 to 29.0 ng/ml, respectively, P < 0.01). However, PRL response to subsequent ICV injection was blunted, probably due to down regulation mechanism. In contrast, ICV injection of vehicle (n = 3) did not cause any changes in plasma PRL concentrations. These results clearly demonstrate that relaxin exerts a central role in modulating PRL secretion in the pig, and RU 486 acts directly on CNS/pituitary to increase PRL secretion.</p>