Characterization of estrogen stimuli sufficient to initiate cyclic luteinizing hormone release in acutely ovariectomized rats.

Estradiol (E)-filled Silastic capsules were implanted subcutaneously to characterize the estrogen stimulus sufficient to initiate cyclic LH secretion in female rats ovariectomized on diestrus 1 of the estrous cycle. Such capsules elevate preoptic area, hypothalamic and hypophysial cell nuclear estrogen receptor levels to proestrous values within 1/2 h following insertion; upon removal of the capsules, nuclear receptor levels decline monotonically to ovariectomized control levels by 8 h in brain and 12 h in pituitary. Three parameters of the E stimulus were studied: latent period, duration, and continuity. E stimuli, short in duration (7-12 h) and discontinuous in nature (3 h pulses 12 or 15 h apart), effectively stimulated LH surges on "proestrus'. However, these stimuli had to begin 30 h prior to the onset of LH release. Such a latent period for estrogen action was not observed when we monitored the ability of the same E stimuli to enhance pituitary responsiveness to GnRH. These studies demonstrate that the "rate-limiting step' for estrogen's positive feedback action is located within the estrogen-sensitive brain circuits controlling GnRH release and defines the temporal characteristics of E stimuli activating these circuits.