Research Interests:

• Reproductive Neuroendocrinology

• Nutritional Modulation of Reproductive Function

• Neuroendocrine Mechanisms Mediating the Stress Response

Reproduction in female mammals is delayed or often inhibited by metabolic deficits.  Energy imbalance caused by reduced food intake, increased energy expenditure, or pharmacological blockade of fuel oxidation inhibits the pituitary-gonadal endocrine axis, disrupts estrous cyclicity, and reduces number and/or birth weigh of offspring.  Although current studies support a central component in the regulation of reproductive hormone secretion by energy homeostasis, the neural mechanisms that link substrate fuel deficits to hypothalamic gonadotropin-releasing hormone (GnRH) release are not known.  Our findings that fourth ventricular administration of 2DG inhibits pituitary luteinizing hormone (LH) release suggest that decreased oxidation of this substrate and generation of metabolic and/or energy products within the periventricular hindbrain activates central mechanisms that suppress reproductive hormone release.  An ongoing multidisciplinary project in our laboratory utilizes neuroanatomical, neuropharmacological, and whole animal physiological techniques to investigate the neural circuitry linking putative glucose 'sensor' sites in the hindbrain to the hypothalamic reproductive neuroendocrine axis.  Our studies utilizing selective opioid receptor antagonists implicate mu opioid receptors in pituitary gonadotropin responses to central glucopenia.  We have found that hypothalamic proopiomelanocortin (POMC) neurons are transactivated by glucoprivic stimuli of hindbrain origin, and that modulatory effects of mu receptor ligands on reproductive function may occur, in part, within septopreoptic structures of demonstrated significance for LH release.  In light of evidence that m receptors inhibit a crucial component of the circuitry activated by estrogen positive-feedback, e.g. the glutamate/NMDA/nitric oxide (NO)/cGMP cascade, we are examining whether mu receptor-expressing neurons in the septopreoptic area respond to hindbrain signaling of metabolic deficits, and if activation of these receptors modifies excitatory amino acid and NO release in this part of the brain.