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Behavioral Neuroendocrinology |
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Cristian Bodo |
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Dept. of Biochemistry and Molec. Genetics 1229 Jordan Hall 1300 Jefferson Park Ave Charlottesville, VA 22908 Phone Number: 434-982-4742 Fax Number: 434-243-8433 Email: ccb6j@virginia.edu Click here for non-science related stuff (i.e. pictures). |
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Research Description: I’m enrolled on the Graduate Program in Neuroscience at UVa, currently finishing my second year at the Rissman lab. The focus of my research so far has been on how steroid hormones affect the mechanisms of sexual differentiation of masculine reproductive behavior in the mouse (Mus musculus). Behaviors related to reproduction (such as partner identification, courtship and mating) are, as it is to be expected, highly dimorphic between the sexes in virtually all species of vertebrates. In the particular case of mammals, these differences have traditionally been considered to be the result of the differential exposure exposure to gonadal hormones secreted during development. The so-called “Organizational Hypothesis”, formulated by the pioneering researchers in the field back in the 60’s, proposed that this gonadal hormones have the ability to stimulate the development of certain neural circuits in the brain that would later be responsible for the exhibition of the appropriate reproductive behaviors by the adult individual according to its sex. Although there is increasing evidence that this may not be the whole story, and viable mechanisms of differentiation based on the genotype of the neural tissue have been postulated (and supported by compelling results in some cases), the action of gonadal steroids is still considered a key factor for understanding the differentiation of reproductive behavior. I have been working with a mouse strain affected by the Tfm syndrome (which stands for Testicular Feminization). This condition is caused by a mutation in the androgen receptor (AR) gene, located on the X chromosome, and therefore with a single copy in male (XY) individuals. Since the Tfm mutation renders the receptor incapable of recognizing its natural ligand, males carrying the mutation develop in complete absence of androgenic signal and their external phenotype is indistinguishable from that of a normal female, illustrating the crucial role of androgen in the development of external reproductive organs. The Tfm syndrome, with different degrees of disruption of the AR function according to the characteristics of the mutation involved, has been described in several species of mammals, including humans. In the mouse, the mutation is thought to disrupt completely the ability of the AR to interact with its ligand, which is the same as to say that the affected individuals are “natural knockouts” for the AR gene. As such, several attempts have been made in the field of behavioral endocrinology to use this model to elucidate the role of androgen in the differentiation of masculine behavior during development, as well as its putative role in the activation of this behavior once the animal has gone through puberty. So far, the results have been contradictory, and I believe that this is due in part to a deficient characterization of the endocrine disruptions that the model exhibits. I’m currently in the process of collecting evidence to support this claim, which, if proven true, would require a reevaluation of the existing literature about the subject. I’m also collaborating with Andrea Kudwa in a project to characterize the role of estrogen receptor beta (ERb) in sexual differentiation. Since its original description in 1996, ERb expression in the CNS has been shown to be widespread, suggesting its involvement in behaviors regulated by estrogen, but no clear function has been assigned to it so far. We have already published results (Temple et al, 2003) showing that knockout male individuals for this receptor (ERbKO) exhibit an impairment in their ability to ejaculate when tested around puberty. Currently we are working on extending the characterization of mating behavior to adult (ERbKO) individuals.
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