Divergent effects of antiprogesterone, RU 486, on progesterone, relaxin, and prolactin secretion in pregnant and hysterectomized pigs with aging corpora lutea

Abstract

Porcine corpora lutea produce progesterone and relaxin during pregnancy and after hysterectomy. Peak amounts of relaxin are released into peripheral blood in both pregnant and hysterectomized animals on about day 113 (estrus = day 0 and term = 114), and this release coincides with an abrupt decrease in the progesterone concentration. 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 (surgery on day 8) once a day (0800 h) on days 111-115 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 less than 0.01). PRL concentrations increased in both groups (9 and 13 ng/ml) and differed significantly from those of the controls (3 ng/ml) (P less than 0.04). RU 486 treatment delayed the time of relaxin peak to days 116.1 and 117.0 in groups 1 and 2 compared with day 114.1 in the controls (P less than 0.01). Pregnant gilts received RU 486 orally once a day (0800 h) 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 less than 0.01). Progesterone decreased abruptly from a pretreatment mean of 11 to less than 0.6 ng/ml during the 2 days that RU 486 was given compared with a shift from 12 to 6 ng/ml during the same period in the controls (P less than 0.01). The time of the relaxin peak was advanced to day 112.1 in RU 486-treated gilts compared with day 113.9 in the controls (P less than 0.01). 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. Disruption of the regulatory loop of progesterone secretion by RU 486 alters the ability of corpora lutea to produce and release peak quantities of relaxin.