Differential Regulation of Gonadotropins in Response to Continuous Infusion of Native Gonadotropin-Releasing Hormone in the Winter Anovulatory Mare and Effects of Treatment With Estradiol-17β

Abstract

We tested the hypotheses that in winter anovulatory mares (1) both chronic daily injections of estradiol-17β (E2) and subcutaneous E2 implants could enhance pituitary secretion of gonadotropins in response to continuous subcutaneous infusion of native gonadotropin-releasing hormone (GnRH); and (2) the secretory pattern of follicle-stimulating hormone (FSH) in response to continuous subcutaneous infusion of native GnRH is similar to that of luteinizing hormone (LH) but differs between mares that develop or fail to develop an estrogen-active, preovulatory follicle. In Experiment 1, 20 winter anovulatory mares (n = 5 per group) in early February received twice-daily injections of corn oil (control) or 5 mg of E2 with or without continuous subcutaneous treatment with native GnRH (100 μg/hr) or received GnRH only for up to 14 days. In Experiment 2, 24 winter anovulatory mares (n = 6 per group) were treated with a full-length (high dose) or quarter-length (low dose) E2 implant (Compudose) in combination with continuous GnRH infusion (100 μg/hr) for up to 28 days or served as sham controls. Mares developing 35-mm follicles were induced to ovulate with human chorionic gonadotropin. Mares not developing a 35-mm follicle within 14 days received a replacement 14-day GnRH pump. In Experiment 1, E2 enhanced the response to GnRH beginning on Day 3, with mean LH greater (P < .001) in GnRH + E2 than in GnRH only and control mares. In Experiment 2, plasma E2 and estrone sulfate were increased in association with the development of a large (35 mm) follicle but did not increase in response to either E2 implant despite marked increases in uterine edema following their insertion. A sustained increase (P < .0001) in plasma LH was observed in all GnRH-treated mares, but this effect was not modified by implant treatment. By Day 28, six of six GnRH, five of six GnRH + low E2, two of six GnRH + high E2, and zero of six control mares developed 35-mm follicles and were induced to ovulate. A marked increase (P < .0001) in plasma FSH was observed within 24 hours in all GnRH-treated mares, returning to baseline by Day 4. In summary, twice-daily injection of 5 mg E2 enhanced pituitary secretion of LH in response to continuous administration of GnRH, but commercial E2 cattle implants failed to duplicate these effects. Continuous infusion of GnRH produced a differential but consistent pattern of FSH secretion (short-term increase) compared with LH (sustained increase). Differences in ovarian responses to GnRH treatment could not be explained by variation in gonadotropin secretion.