Research:

My research program is aimed at understanding how hormones regulate brain functions and behaviors, from the level of the organism to molecular structures. Currently, three major projects focus on (1) the non-genomic mechanisms of action for corticosteroids that control brain functions and behaviors during acute stress, (2) the neurobiology of the vasotocin /vasopressin peptide systems that control social behaviors, and (3) the neuroendocrine responses to pheromones that induce female sexual receptivity. These research projects utilize amphibian research models, taking advantage of the simplified brain structures and functions of amphibians and their reliable behavioral responses to hormone manipulations.

Non-genomic mechanisms of action for corticosteroids. This research project began with the observation that corticosterone, the primary adrenal steroid hormone secreted during stress, rapidly and potently suppresses courtship behaviors in an amphibian. This response is too fast to be explained by the classical genomic model for steroid hormones. To investigate the receptor mechanisms of the rapid response to corticosterone, we used ligand-binding assays with neuronal membranes and discovered a membrane-associated corticosterone receptor (mCR). We subsequently demonstrated that this mCR is functional, controlling rapid behavioral responses during acute stress. Pharmacological characterization of the mCR shows that it is distinct from intracellular glucocorticoid receptor and fits the model for receptors in the G-protein coupled receptor (GPCR) family. Our recent studies characterized the mCR biochemically using a variety of chromatographic systems, photo-affinity labeling techniques, and SDS-PAGE and found that the purified receptor protein is glycosylated and has the molecular mass of known receptors in the GPCR family. This information, plus other independent evidence, suggests that the mCR is structurally and functionally related to opioid-like receptors. With support from an NIMH research grant, we are continuing our study of the mCR, investigating its molecular identity using RACE-PCR cloning and in vitro expression techniques. Behavioral assays and ligand-binding studies are being used to verify congruence between the cloned receptor and the endogenous mCR.

Neurobiology of the vasopressin/vasotocin peptide system. This research project builds on our early findings that vasotocin (the non-mammalian equivalent of vasopressin) enhances male courtship behaviors by acting within the brain as a neuromodulator. Behavioral responses to vasotocin depend on testicular androgens. In studies using immunohistochemistry and in situ hybridization histochemistry, we discovered that vasotocin is synthesized in numerous sites in the brain and that a subset of the vasotocin cell groups are sexually dimorphic. There are greater numbers of vasotocin-containing neurons in males than in females in the three brain areas that are known to be involved in male behaviors (amygdala, bed nucleus of the stria terminalis, and anterior preoptic area). Now we are investigating specific questions about the actions of sex steroid hormones on the vasotocin system to understand better how male- and female-specific behaviors are regulated. To investigate the structural and functional characteristics of the vasotocin receptor, we are using RACE-PCR strategy to obtain the full-length cDNA sequence for the V1a-like vasotocin receptor and then expression systems to pharmacologically characterize the receptor. To investigate the hypothesis that vasotocin enhances social behaviors by modulating sensorimotor processing of specific sensory stimuli, we are using behavioral assays and neurophysiology to investigate the effects of vasotocin on species-specific sexual stimuli from different sensory modalities (olfactory, visual, and tactile sexual stimuli). We also are starting to investigate the functional relationships between vasotocin and corticosterone in the control of social behaviors.

Neuroendocrinology of pheromones. This research project uses an identified sex pheromone that functions to enhance female sexual receptivity in a species of Plethodon salamander. To investigate the effects of this pheromone on neuroendocrine responses, we are using Real Time PCR to quantify changes in the expression of specific genes in females that have been exposed to pheromone extract. Other studies are using in situ hybridization histochemistry procedures to identify neurons that after pheromone administration show increases in cFOS mRNA, which serve as an indirect measure of neuronal activity. This NSF funded research project is one aspect of a larger project involving nine senior scientists (Houck, Arnold, and Moore from OSU); the overall goal of this project is to understand better the evolution of pheromone signaling systems.

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This page was last edited on April 4, 2002