LACK OF GONADOTROPIN-POSITIVE FEEDBACK IN THE MALE-RAT IS ASSOCIATED WITH LACK OF ESTROGEN-INDUCED SYNAPTIC PLASTICITY IN THE ARCUATE NUCLEUS

We have demonstrated that estrogen induces synaptic reorganization in the hypothalamic arcuate nucleus of female rats during the ovarian cyc le and proposed that estrogen-induced synaptic retraction plays a role in the disinhibition of gonadotropin secretion that occurs during the afternoon of proestrus. This so-called positive feedback of gonadotro pins is developmentally determined. It is present in female rats and a bsent in males. To confirm the role of the estrogen-induced synaptic r etraction in positive feedback, we tested whether administration of es trogen to male rats also fails to induce synaptic remodeling of the ar cuate nucleus. Male and female rats were gonadectomized and studied as follows. One month following gonadectomy, animals received either a s ingle injection of estradiol (100 mu g/animal in sesame oil; 12 males and 12 females) or vehicle (6 males and 6 females). Twenty-four hours following injections, all animals in the vehicle-injected group and 6 animals of each sex in the treatment groups were sacrificed, while the rest of the animals were killed 48 h following the hormone injections (6 per group). As expected, quantitative electron microscopic analysi s of the female arcuate nuclei revealed that compared to oil-injected controls, estradiol induced drastic decreases in the overall synapse c ounts by 24 h (121 +/- 10 vs. 74 +/- 5 synapses/1,000 mu m membrane; p < 0.05). Synaptic counts had recovered to control levels by 48 h. On the contrary, in males, estradiol treatment did not cause changes in t he total synapse counts at either time. As a further control, the lack of an estrogen-induced gonadotropin surge in long-term castrate males was also confirmed. Our study confirmed that in males estradiol does not alter the net synaptology of the arcuate nucleus or cause gonadotr opin positive feedback. This is in clear contradistinction to females which show both synaptic plasticity and gonadotropin-positive feedback upon receiving exogenous or endogenous estrogen. The lack of estrogen -induced synaptic plasticity may be an underlying mechanism in the abo lishment of positive gonadotropin, feedback in developing males and th e development of constant estrus in aging female rats.