Inhibitory effects of a gonadotropin-releasing hormone agonist on the luteal synthesis of progesterone, estradiol receptors, and prolactin surges during early pregnancy.

Our recent studies demonstrated that the continuous administration of a GnRH agonist (GnRH-Ag; WY 40972) induces abortion in rats by suppressing plasma progesterone (P) levels within 24 h. This fall in P levels is not accompanied by a fall in ovarian venous plasma testosterone (T) or estradiol (E) levels. In this study an attempt was made 1) to determine whether the suppression of P by GnRH-Ag is due to decreased estrogen present in the corpora lutea (CL) and/or a decrease in luteal receptors of E, and 2) to investigate the effects of GnRH-Ag on the nocturnal surges of PRL. Rats were treated continuously on days 7-11 of pregnancy with 5 micrograms/day GnRH-Ag using an osmotic minipump. Ovarian blood samples were obtained on day 8; at autopsy CL were harvested and incubated with medium 199 for 4 h at 37 C under an atmosphere of 95% oxygen-5% carbon-dioxide. Additional rats were killed on day 8 or 10; CL were isolated from the ovary and pooled within the group for the measurement of nuclear and cytosolic E receptors. In other experiments, on days 8, 9, 10, and 11 of pregnancy, blood samples (0.3 ml) were collected via an indwelling intraatrial Silastic cannula at 0330, 0500, or 0600 h for the measurement of PRL and P. While the net synthesis of P by CL in the GnRH-Ag-treated rats decreased to 48 +/- 12 from 224 +/- 47 ng/CL in controls, T and E levels were not different from their respective control values. Steroid levels in ovarian venous plasma reflected a similar response. Nuclear E receptors levels were 82 and 80 in controls and 39 and 41 fmol/mg DNA in the treated group on days 8 and 10, respectively. Nocturnal surges of PRL in plasma were detected at 0330 h in controls as well as in treated rats. However, plasma PRL levels at 0330 h were 101 +/- 24, 120 +/- 22, 196 +/- 40, and 103 +/- 13 ng/ml in controls and 44 +/- 8, 50 +/- 10, 29 +/- 13, and 20 +/- 9 in the GnRH-Ag-treated group on days 8, 9, 10, and 11, respectively. These results suggest that GnRH-Ag has no effect on the ability of the luteal synthesis of T and E and that the antipregnancy effect of GnRH-Ag may be at the level of the CL due to the direct inhibitory effect of GnRH-Ag on the luteal synthesis of P, which, in turn, results in decreased nocturnal surges of PRL and a fall in E receptors in the CL. Alternatively, GnRH-Ag treatment could suppress ovarian or luteal receptors for PRL, which, in turn, lower luteal E receptors, leading to a fall in luteal synthesis and release of P.