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Sex and the Developing Brain: Suppression of Neuronal Estrogen Sensitivity by Developmental Androgen Exposure

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Abstract

The developmental effects of androgen play a central role in sexual differentiation of the mammalian central nervous system. The cellular mechanisms responsible for mediating these effects remain incompletely understood. A considerable amount of evidence has accumulated indicating that one of the earliest detectable events in the mechanism of sexual differentiation is a selective and permanent reduction in estrogen receptor concentrations in specific regions of the brain. Using quantitative autoradiographic methods, it has been possible to precisely map the regional distribution of estrogen receptors in the brains of male and female rats, as well as to study the development of sexual dimorphisms in receptor distribution. Despite previous data suggesting that the left and right sides of the brain may be differentially responsive to early androgen exposure, there is no significant right-left asymmetry in estrogen receptor distribution, in either sex. Significant sex differences in receptor density are, however, observed in several regions of the preoptic area, the bed nucleus of the stria terminalis and the ventromedial nucleus of the hypothalamus, particularly in its most rostral and caudal aspects. In the periventricular preoptic area of the female, highest estrogen receptor density occurs in the anteroventral periventricular region: binding in this region is reduced by approximately 50% in the male, as compared to the female. These data are consistent with the hypothesis that androgen-induced defeminization of feminine behavioral and neuroendocrine responses to estrogen may involve selective reductions in the estrogen sensitivity of critical components of the neural circuitry regulating these responses, mediated in part through a reduction in estrogen receptor biosynthesis.

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Authors and Affiliations

  1. Division of Reproductive Science, The Toronto Hospital Research Institute and Department of Physiology, University of Toronto, Canada

    Neil J. MacLusky, Deborah A. Bowlby & Theodore J. Brown

  2. Department of Zoology, University of Toronto, Canada

    Theodore J. Brown

  3. School of Pharmacy and Environmental Toxicology Center, University of Wisconsin, Madison, Wisconsin, 53706

    Richard E. Peterson

  4. Department of Obstetrics and Gynecology, Yale University, New Haven, Connecticut

    Richard B. Hochberg

Authors
  1. Neil J. MacLusky
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  2. Deborah A. Bowlby
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  3. Theodore J. Brown
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  4. Richard E. Peterson
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  5. Richard B. Hochberg
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MacLusky, N.J., Bowlby, D.A., Brown, T.J. et al. Sex and the Developing Brain: Suppression of Neuronal Estrogen Sensitivity by Developmental Androgen Exposure. Neurochem Res 22, 1395–1414 (1997). https://doi.org/10.1023/A:1022027408234

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