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Location, location, location: Genetic regulation of neural sex differences

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Abstract

Sex differences in many behaviors such as cognition, mood, and motor skills are well-documented in animals and humans and are regulated by many neural circuits. Sexual dimorphisms within cell populations in these circuits play critical roles in the production of these behavioral dichotomies. Here we focus on three proteins that have well described sexual dimorphisms; calbindin-D28k, a calcium binding protein, tyrosine hydroxylase, the rate limiting enzyme involved in dopamine synthesis and vasopressin, a neuropeptide with central and peripheral sites of action. We describe the sex differences in subpopulations of these proteins, with particular emphasis on laboratory mice. Our thrust is to examine genetic bases of sex differences and how the use of genetically modified models has advanced our understanding of this topic. Regional sex differences in the expression of these three proteins are driven by sex chromosome complement, steroid receptors or in some instances both. While studies of sex differences attributable to sex chromosome genes are still few in number it is exciting to note that this variable factors into expression differences for all three of these proteins. Different genetic mechanisms, which elaborate sex differences, may be employed stochastically in different cell populations. Alternately, general patterns involving the timing of differentiation of the sex differences, relative to the “critical period” in hormonal differences between males and female neonates may emerge. In conclusion, future directions in this area should include examination of the importance of location, timing, steroidal receptor/sex chromosome gene synergy and epigenetics in molding neural sex differences.

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Acknowledgements

We are grateful to Paul Bonthuis for constructive comments on this manuscript. The work by the authors reported here was supported by National Institutes of Health R01NS055218.

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  1. Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, PO Box 800733, Charlottesville, VA, 22908, USA

    Jean LeBeau Abel & Emilie F. Rissman

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  1. Jean LeBeau Abel
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  2. Emilie F. Rissman
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Correspondence to Jean LeBeau Abel.

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Abel, J.L., Rissman, E.F. Location, location, location: Genetic regulation of neural sex differences. Rev Endocr Metab Disord 13, 151–161 (2012). https://doi.org/10.1007/s11154-011-9186-0

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