Progesterone can block transmission of the estradiol-induced signal for luteinizing hormone surge generation during a specific period of time immediately after activation of the gonadotropin-releasing hormone surge-generating system

The preovulatory GnRH/LH surge in the ewe is stimulated by a rise in the ci rculating estradiol concentration that occurs in conjunction with preovulat ory ovarian follicle development. In the presence of high levels of progest erone, such as during the luteal phase of the estrous/menstrual cycle, the stimulatory effects of elevated estradiol on GnRH/LH secretion are blocked. Recent work in the ewe has shown that a relatively short period of estradi ol exposure can stimulate a GnRH/LH surge that begins after estrogenic supp ort has been removed. This result suggests that surge generation is charact erized by an estradiol-dependent period (during which the signal is read) a nd an estradiol-independent period (during which a cascade of neuronal even ts transmits the stimulatory signal to the GnRH neurosecretory system, whic h releases a surge of GnRH). In this series of studies, we addressed the hy pothesis that progesterone can black transmission of the stimulatory estrad iol signal after it has been read. Nine ovariectomized ewes were run throug h repeated artificial estrous cycles by sequential addition and removal of exogenous steroids. In study one, ewes received three treatments in a rando mized cross-over design. Exposure to a follicular phase estradiol concentra tion for 10 h (positive control treatment) stimulated an LH surge in all ew es, as determined in hourly jugular blood samples. Maintenance of luteal ph ase progesterone concentrations throughout the artificial follicular phase (2 x CIDR-G devices, negative control) blocked the stimulatory effects of a 10-h estradiol signal, and no ewes that received this treatment expressed an LH surge. Ln the experimental group, exposure to luteal phase levels of progesterone, during the period after the surge generating system had been activated by estradiol, blocked the LH surge in six of nine ewes. This resu lt demonstrates that progesterone can block the surge, even when applied af ter the surge-generating system has been activated and, therefore, that it inhibits either the transmission of the estradiol signal and/or the release of the GnRH/LH surge. In study 2, we assessed whether sensitivity to the i nhibitory effects of progesterone was confined to a specific stage of the t ransmission of the estradiol signal. Eight ewes were exposed to four treatm ents, over successive artificial estrous cycles. Positive and negative cont rols were similar to those described in Study 1, except the duration of the stimulatory estradiol signal was reduced to 8 h. The two experimental grou ps consisted of an EARLY P (progesterone) treatment, in which progesterone was given from hours 8-13 after estradiol insertion (immediately after estr adiol removal), and a LATE P treatment, in which progesterone was given fro m hours 13-18 (immediately before LH surge secretion). As expected, LH surg es were stimulated and blocked, in response to the positive and negative co ntrols, respectively. Whereas the EARLY P treatment blocked the LH surge in seven of eight ewes, the LATE P treatment was only successful in inhibitin g a surge in one of eight animals. This result demonstrates that progestero ne can block the estradiol-induced surge-generating signal soon after the o nset of signal transmission (immediately after estradiol removal) but not d uring the later stages of signal transmission (at the time of GnRH/LH surge onset).