One project in our laboratory investigates the mechanisms by which estrogen regulates the development and adult functioning of neural circuits that control reproduction. In early studies we identified a specific brain region, the anteroventral periventricular nucleus (AVPV) as a site in which estrogen acts to trigger the brain signal for ovulation. We recently made the important discovery that in this brain region, the inhibitory neurotransmitter, GABA, is released from the same cells that release glutamate, a stimulatory neurotransmitter. More importantly, these dual-function neurons are directly regulated by estrogen and are found predominantly in females. We are currently examining whether estrogen initiates the brain signal for ovulation by altering the balance between GABA and glutamate release. In addition, we are investigating developmental processes responsible for sex differences in the incidence of these unusual neurons.

A second project in the laboratory investigates how a specific class of environmental endocrine disruptors, dioxins, interferes with sexual differentiation of the brain. A single exposure to dioxin during development permanently alters brain development such that males show feminine patterns of gonadotropin release in adulthood. Dioxins exert their effects through activation of the arylhydrocarbon receptor (AhR) and we found that genes encoding this receptor and its companion proteins are expressed in the AVPV, the brain region responsible for female-typical goandotropin release patterns. More recently we found that in this region, the AhR is expressed in dual-function GABA/glutamate neurons found specifically in females. We are currently testing the hypothesis that developmental exposure to dioxins interferes with sexual differentiation of gonadotropin release patterns by altering the sex-specific development of GABA/glutamate neurons in the AVPV.

For our studies, we use a wide range of in vivo and in vitro approaches including: dual-label in situ hybridization histochemistry, immunocytochemistry with confocal analysis, HPLC (electrochemical detection), cell cultures, transient transfection analysis of promoter activity, Northern, southern and western blots, real-time PCR and PCR cloning, as well as genomics and proteomics techniques.