STIMULATION OF PROLACTIN SECRETION IN THE PIG - CENTRAL EFFECTS OF RELAXIN AND THE ANTIPROGESTERONE RU-486

Our previous study has shown that oral administration of a potent progesterone antagonist, RU 486, caused a marked elevation of plasma concentrations of both PRL and progesterone in hysterectomized pigs bearing aging corpora lutea. Hysterectomized pigs (hysterectomy performed on day 8; estrus = day 0) were subjected to cranial surgery for chronic placement of a head-mounted stereotaxic apparatus for intracerebroventricular (icv) administration of relaxin (300 U once daily on days 111 and 113; n = 6) and RU 486 (4 mg once daily on days 111, 113, and 115; n = 5) to test whether relaxin and RU 486 exert their actions within the central nervous system and/or pituitary gland to affect PRL and GH secretion. Control pigs (n = 3) received icv injection of vehicle. Intensive blood sampling revealed that icv injection of relaxin on day 111 markedly increased the plasma PRL concentration from 8 to 38 ng/ml within 10 min (P < 0.01). An identical icv injection of relaxin on day 113 caused only a modest increase in PRL, but the overall mean concentration of PRL after relaxin treatment was greater than that before treatment (14 vs. 8 ng/ml; P < 0.05). Intracerebroventricular injection of RU 486 on day 111 greatly elevated plasma PRL. The increase in PRL lasted more than 2 h, with several peak increases of 18-29 ng/ml (P < 0.01). The PRL response to subsequent icv infusion of RU 486 on days 113 and 115 was blunted, but the overall mean concentration of PRI, (14 ng/ml) after icv injection of RU 486 remained greater (P < 0.01) than that before treatment (9 ng/ml). In contrast, PRL concentrations in the control group remained unchanged after injection. Plasma concentrations of GH, relaxin, and progesterone were significantly altered in neither hormone- nor vehicle-treated groups during this brief period of sequential blood sampling. This study provides strong evidence that relaxin has a central role in modulating PRL secretion in the pig. In addition, the antagonistic effects on progesterone receptor by RU 486 in the central nervous system and/or pituitary gland caused an abrupt increase in PRL secretion in these hysterectomized gilts.