Neuroestradiol in the Stalk Median Eminence of Female Rhesus Macaques Decreases in Association With Puberty Onset

In primates, despite the fact that GnRH neurons are mature at birth, a gonadal steroid independent central inhibition restrains the initiation of puberty. The neural substrates responsible for this central inhibition, however, are unclear. In this study, we tested the hypothesis that neuroestradiol release in the hypothalamus decreases prior to the pubertal increase in GnRH release. We found that in female monkeys at the prepubertal stage, when GnRH release was low, estradiol (E2) levels in the stalk-median eminence of the hypothalamus were higher than those in older, early pubertal females in which nocturnal GnRH release begins to increase. Furthermore, estrone (E1) levels were higher in the stalk-median eminence of prepubertal and early pubertal monkeys compared with midpubertal monkeys, which have the highest GnRH release. The elevated E2 and E1 levels at the prepubertal stage are likely hypothalamic in origin because circulating E2 and E1 levels in prepubertal and early pubertal monkeys were much lower than those in midpubertal monkeys. Heightened synthesis and release of neuroestradiol during the prepubertal period and subsequent reduction at puberty onset indicate possible roles for neuroestradiol in central inhibition of GnRH release. The mechanism governing the reduction in neuroestradiol synthesis at puberty onset remains to be determined.