title: 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.
authors.affiliation: Wisconsin National Primate Research Center, and Department of Pediatrics, University of Wisconsin, Madison, Wisconsin 53715.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Kenealy
authors.forename: Amita
authors.initials: A
authors.lastname: Kapoor
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Guerriero
authors.forename: Kim L
authors.initials: KL
authors.lastname: Keen
authors.forename: James P
authors.initials: JP
authors.lastname: Garcia
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Kurian
authors.forename: Toni E
authors.initials: TE
authors.lastname: Ziegler
authors.forename: Ei
authors.initials: E
authors.lastname: Terasawa
mesh_terms: D000818:Animals; D047072:Aromatase Inhibitors / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D007033:Hypothalamus, Middle / Q000187:drug effects / Q000378:metabolism; D000077289:Letrozole; D008253:Macaca mulatta; D013058:Mass Spectrometry; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism; D017551:Microdialysis; D009570:Nitriles / Q000494:pharmacology; D010052:Ovariectomy; D011863:Radioimmunoassay; D014230:Triazoles / Q000494:pharmacology
chemical_list: D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; C074283:estradiol 3-benzoate; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D000077289:Letrozole