Evidence that Estradiol Induces the Preovulatory LH Surge in Cattle by Increasing Pituitary Sensitivity to LHRH and then Increasing LHRH Release*

Abstract

The objectives of these studies were to determine 1) the influence of estradiol on the ability of the pituitary gland to release LH in response to LHRH in vivo, and 2) whether LHRH is required to cause the preovulatory LH surge in cattle. To minimize the confounding effect of endogenous LHRH or LHRH-induced LH release, we used the estradiol-treated steer as a model for the cow. The rationale for this choice is that estradiol does not normally cause an LH surge in steers, but it does exert a negative feedback effect inhibiting LHRH secretion. In the first experiment, an LH surge was induced in steers by injecting 1 μg LHRH at 20-min intervals between 12 and 20 h after estradiol. This surge resembled the preovulatory LH surge in cows with respect to both duration (10 h) and amplitude (49 ng/ml). After the peak, LH concentrations returned to baseline despite continued LHRH injections. In control steers given oil, repetitive injections of LHRH increased serum LH to only 13 ng/ml. In a second experiment, steers were given 1 μg LHRH at 20-min intervals beginning 2, 8, 12, or 20 h after estradiol. Two hours after beginning LHRH injections, serum LH had increased to 19 ng/ml in oil-treated controls. The corresponding values for steers injected with LHRH beginning 2, 8, 12, or 20 h after estradiol were 6, 25, 35, and 38 ng/ml, respectively. Thus, estradiol first decreased, then increased LHRH-induced LH release. To determine whether estradiol alters LHRH-induced LH release in ovariectomized (ovx) cows as it does in steers, ovx cows were given 1 μg LHRH every 20 min beginning 2 or 8 h after estradiol. As in steers, peak LH release induced by LHRH in ovx cows was greater (P < 0.005) 8 h after estradiol (62 ng/ml) than after oil (11 ng/ml). The pattern of LH secretion in the estradiol-treated cows was indistinguishable from a normal preovulatory LH surge. In contrast, when LHRH was injected beginning 2 h after estradiol, the LH increments 2–4 h after estradiol (1–5 ng/ml) were less (P < 0.005) than for oil-treated controls (6 ng/ml). However, this inhibitory phase was quickly reversed, such that serum LH reached 47 ng/ml at 8 h after estradiol. In conclusion, increasing serum concentrations of estradiol first reduced, then increased the ability of the pituitary to release LH in response to LHRH in cattle. Furthermore, the pituitary was as responsive to LHRH 5–15 h before the time of the LH surge as it was during the surge. However, although the pituitary is responsive to LHRH, concentrations of LH in serum remain at baseline levels until the time of the LH surge, suggesting that estradiol inhibits LHRH secretion. Our results suggest that the onset of the LH surge is triggered by resumption of LHRH secretion. Finally, the LH surge terminated even though LHRH administrations continued.