Date of Award

8-3-2006

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

First Advisor

Dr. Andrew N. Clancy - Chair

Second Advisor

Dr. Sarah L. Pallas

Third Advisor

Dr. Timothy J. Bartness

Fourth Advisor

Dr. H. Elliott Albers

Abstract

Male rat mating is a suite of individual behaviors mediated by the actions of two metabolites of testosterone (T), dihydrotestosterone (DHT) and estradiol (E2), on the brain. Individually, neither metabolite fully maintains or restores mating in castrated males, but both combined are as effective as T. Two hormone-responsive areas of the brain, the medial preoptic area (MPO) and the medial amygdala (MEA), are crucial for mating. These studies ask: by what mechanism(s) does E2 act in the MPO and MEA? We blocked the conversion of T to E2 in the MEA of intact male rats and sexual behavior was not maintained. We then infused antisense oligodeoxynucleotides (ODNs) to estrogen receptor-alpha (ER-á) mRNA bilaterally to the MPO or the MEA of intact male rats to block ER-á expression. ODN infusion of the MPO attenuated mating but infusion of the MEA had no effect. These results suggest that ER-á is the behaviorally relevant estrogen receptor (ER) in the MPO but not in the MEA. ER was originally described in the cytoplasm and nucleus of cells. Recently plasma membrane associated ERs (mER) have been reported. We conjugated E2 to Bovine Serum Albumin (BSA-E2), a large protein that will not penetrate the plasma membrane, thus restricting the action of E2 to mER, and chronically delivered it to the MPO and MEA. BSA-E2 maintained mating if put in the MPO, but not in the MEA, suggesting a surface action of E2 is sufficient in the MPO. The MPO and MEA are reciprocally connected and probably constitute elements of a larger, steroid-responsive neural network that mediates male mating behavior. To begin to describe this purported circuit, we injected Pseudorabies virus (PRV) into the prostate gland and dually labeled PRV-immunoreactive cells for ER or androgen receptors. We found dual labeling in a forebrain diencephalic circuit that includes the MPO, the medial preoptic nucleus, bed nucleus of stria terminalis, the zona incerta, the periaqueductal gray and other areas that presumably mediate both autonomic and motor aspects of male mating. Together, the results of these studies begin to elucidate locations and mechanisms of E2 mediation of male sexual behavior.

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Biology Commons

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