The neuroendocrine signal for ovulation: Definition and regulation.

Abstract

Ovulation is caused by a surge of luteinizing hormone (LH) release from the pituitary. The nature and regulation of the neuroendocrine signal for ovulation were defined in sheep. First, the neuroendocrine factor regulating reproduction, gonadotropin-releasing hormone (GnRH), was measured in pituitary portal blood during the preovulatory period. Low frequency GnRH pulses occurred during the luteal phase. Pulse frequency increased and amplitude decreased during the follicular phase. A robust GnRH surge began coincident with the preovulatory LH surge; the GnRH surge outlasted that of LH by several hours. Whether estradiol elicits these changes in GnRH release was investigated using a physiologic model for the follicular phase, in which estradiol was manipulated (removed or increased to peak follicular phase level) 16 hours after progesterone removal. Following estradiol removal, GnRH and LH were secreted in coincident bursts. Estradiol had a biphasic effect on GnRH release: first, it suppressed pulsatile GnRH release, second, it induced a GnRH surge. These results support the hypothesis estradiol regulates GnRH release, and that this central action is part of the mechanism by which estradiol induces the LH surge. Two studies were performed to examine the mechanism by which estradiol evokes the GnRH surge. Very frequent samples of pituitary portal blood were obtained to determine the moment-to-moment GnRH-release pattern during the surge. Estradiol shifted to pattern of GnRH release, permitting continuous elevation in portal blood, possibly by desynchronizing GnRH neurons, accelerating pulses beyond resolution of the technique, or recruiting an asynchronous surge-specific population of GnRH neurons. The latter was investigated in the final study in which active cells were localized by immunocytochemical staining for cFos--a marker of neural activity. A striking induction of cFos expression occurred in GnRH neurons during the surge. These cells, however, were not located in an anatomically distinct region, precluding identification of a surge-specific population of GnRH neurons. A surge-specific population of non-GnRH-positive cells was identified, raising the possibility these cells convey the positive feedback signal to the GnRH neurons. We conclude estradiol activates several neural populations and thereby induces the GnRH surge, which is a prerequisite neuroendocrine signal for ovulation in sheep.