The neurochemical mechanisms underlying hindbrain glucoprivic suppression of the luteinizing hormone (LH) surge are not known. A body of experimental evidence supports the view that gonadal steroid positive-feedback action on the reproductive neuroendocrine axis relieves tonic GABAergic inhibition of gonadotropin-releasing hormone neurons by diminishing preoptic release of this neurotransmitter. The present studies evaluated the hypothesis that hindbrain glucoprivic attenuation of the LH surge may be correlated with site-specific modifications in gonadal steroid suppression of γ-aminobutyric acid release in this region of the brain. Individual septopreoptic loci were microdissected from the brains of estrogen, progesterone-primed ovariectomized female rats injected with the glucose antimetabolite, 5-thioglucose (5-TG), or vehicle into the caudal fourth ventricle during the ascending phase of the surge, and analyzed by high-performance liquid chromatography. The data show that 5- TG administration increased GABA release within the rostral preoptic area (rPO), anteroventral periventricular nucleus (AVPV), and median preoptic nucleus (MEPO), relative to the vehicle-treated controls, but did not alter neurotransmitter release in other structures evaluated. The rate of GABA turnover in each brain site was equivalent between animals injected with the µ opioid receptor antagonist CTOP and 5-TG versus their vehicle-treated controls. These results constitute novel evidence for site-specific modulation of steroid positive-feedback suppression of this inhibitory neurotransmitter by caudal hindbrain signaling of glucose insufficiency, and support the need for neurochemical characterization of glucoprivic-sensitive afferent input to GABAergic neurons terminating within the rPO, AVPV, and MEPO, as well as the relevance of enhanced local GABA release for reproductive neuroendocrine function.

Keywords:
Glucose, Preoptic area, Periventricular nucleus, Ovariectomy, Preoptic nucleus, γ-Aminobutyric acid, Opioid receptors, Gonadotropins, Gonadal steroids
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