Neuroestradiol in the Hypothalamus Contributes to the Regulation of Gonadotropin Releasing Hormone Release

Abstract

Release of gonadotropin releasing hormone (GnRH) from the medial basal hypothalamus (MBH)/median eminence region (S-ME) is essential for normal reproductive function. GnRH release is profoundly regulated by the negative and positive feedback effects of ovarian estradiol (E₂). Here we report that neuroestradiol, released in the S-ME, also directly influences GnRH release in ovariectomized female monkeys, in which the ovarian source of E₂ is removed. We found that (1) brief infusion of E₂ benzoate (EB) to the S-ME rapidly stimulated release of GnRH and E₂ in the S-ME of ovariectomized monkeys, (2) electrical stimulation of the MBH resulted in GnRH release as well as E₂ release, and (3) direct infusion of an aromatase inhibitor to the S-ME suppressed spontaneous GnRH release as well as the EB-induced release of GnRH and E₂. These findings reveal the importance of neuroestradiol as a neurotransmitter in regulation of GnRH release. How circulating ovarian E₂ interacts with hypothalamic neuroestrogens in the control of GnRH release remains to be investigated.