Effect of graded doses of gonadotrophin-releasing hormone on serum LH concentrations in mares in various reproductive states: comparison with endogenously generated LH pulses

Abstract

ABSTRACT Luteinizing hormone release induced by a range of small (3·3–33 μg) and large (300–500 μg) i.v. doses of gonadotrophin-releasing hormone (GnRH) was measured in acyclic (n = 4), luteal phase (n = 3) and follicular phase (n = 5) mares and compared with endogenously generated LH pulses in the same reproductive states. Extrapolation from log–linear dose–response curves showed that an LH pulse comparable to an endogenous one would be simulated by i.v. injection of 7·0 (n = 4) and 4·1 (n = 6) μg GnRH in luteal and follicular phase mares respectively; a much smaller dose than the 500 μg usually given clinically or experimentally. In acyclic mares (n = 4), LH pulses occurred too infrequently to be characterized. At small doses of GnRH the amount of LH released by the same dose was similar in all three reproductive states, although the steroid hormone milieu differed markedly. This implies that observed differences between states in mean (± s.e.m.) serum LH concentrations (0·7 ± 0·01, 1·2 ± 0·03 and 11·6 ± 0·33 (μg/l) in acyclic, luteal and follicular phase mares respectively) were produced by differences in GnRH pulse frequency and/or amplitude and not by steroid-mediated changes in pituitary response to GnRH. In acyclic, luteal and follicular phase mares, LH pulse frequency was: immeasurably low, 0·09 and 1·14 pulses/h respectively, which supports the important contribution of pulse frequency to determining mean LH concentration. The LH response to large doses of GnRH was significantly greater in the luteal than in the follicular phase, and was greater than the response to 33 μg in the luteal phase but not in the other two states. Thus, to a large but not to a small dose of GnRH, the pituitary appeared most responsive in the luteal phase. Therefore, in studies of the physiology of the hypothalamic-pituitary system, small doses of GnRH, which induce physiologically sized LH responses, may be preferred to large doses, which result in a level of stimulation to which the pituitary is never naturally exposed and to which it may respond in a non-physiological manner. J. Endocr. (1986) 110, 19–26