SYNAPTIC REMODELING IN THE ARCUATE NUCLEUS DURING THE ESTROUS-CYCLE IS INDUCED BY ESTROGEN AND PRECEDES THE PREOVULATORY GONADOTROPIN SURGE

We have shown that the ovarian cycle is accompanied by a fall in the a xosomatic synapses on randomly selected neurons of the arcuate nucleus by the morning of estrus, with a return to the preovulatory levels by the morning of metestrus, indicating a possible role in positive feed back. However, it remains to be proven that the circulating estradiol is the actual regulator of this physiological synaptic plasticity, or that estrogen-induced synaptic retraction precedes in the surge of gon adotropins at midcycle. To resolve these questions, we used an estradi ol-immunoneutralization protocol and studied arcuate nucleus axosomati c synapses during the critical points of the estrous cycle. In additio n to blocking positive feedback, estrogen immunoneutralization abolish ed synaptic retraction in the arcuate nucleus. As a positive control, the nonbinding estrogen diethylstilbestrol maintained the gonadotropin surge and synaptic retraction in the anti-estradiol-treated animals. Furthermore, in the diluent-treated cycling control females, the synap tic retraction was found to precede the preovulatory LH surge. We demo nstrated that the midcycle synaptic retraction of arcuate nucleus syna pses is induced by the preovulatory estradiol surge, and that these mo rphological events precede the preovulatory gonadotropin surge. Taken together, these observations strongly suggest that the hypothalamic me chanism underlying the physiological disinhibition of gonadotropins at midcycle (positive feedback) requires estrogen-induced synaptic retra ction in the arcuate nucleus.