Trends in Endocrinology & Metabolism

Trends in Endocrinology & Metabolism

Volume 15, Issue 1, January–February 2004, Pages 6-11
Journal home page for Trends in Endocrinology & Metabolism

Are XX and XY brain cells intrinsically different?

https://doi.org/10.1016/j.tem.2003.11.001Get rights and content

Abstract

In mammals and birds, the sex of the gonads is determined by genes on the sex chromosomes. For example, the mammalian Y-linked gene Sry causes testis differentiation. The testes then secrete testosterone, which acts on the brain (often after conversion to estradiol) to cause masculine patterns of development. If this were the only reason for sex differences in neural development, then XX and XY brain cells would have to be deemed otherwise equivalent. This equivalence is doubtful because of recent experimental results demonstrating that some XX and XY tissues, including the brain, are sexually dimorphic even when they develop in a similar endocrine environment. Although X and Y genes probably influence brain phenotype in a sex-specific manner, much more information is needed to identify the magnitude and character of these effects.

Section snippets

Sex differences in sex chromosome gene expression

XX and XY cells have a different complement of genes, which might reasonably lead the cells to have intrinsic differences, irrespective of their hormonal environment. First, XY cells have Y-linked genes that are absent in XX cells. The potential impact of Y genes is restricted because the mammalian Y chromosome is gene poor (only 27 different proteins appear to be encoded by the human Y chromosome [10]), and because the expression of several Y genes is limited to a single cell type (male germ

Sex chromosome induction of sex differences in tissues other than the gonads

The information about X and Y gene dosage forms an important foundation for understanding the potential for differences between XX and XY cells that are independent of the hormonal environment. However, the central question is whether these cells differ in form or function because of X and Y gene expression within the cells themselves. One of the first reports suggesting such a difference was that male and female mammalian embryos develop at a different rate at ages before the onset of gonadal

Mouse model systems for varying sex chromosome complement

The field of sex determination, however, has provided mouse model systems that are particularly useful because the genetic sex of cells is made independent of gonadal phenotype. When Sry was identified as the testis-determining gene, it became possible to identify mice that had a Y chromosome lacking Sry (the Y− chromosome) 31, 32, producing XY− mice with a male genome (except for the absence of Sry), but which have ovaries and hence are called females here. Sry has been added back into these

Studies of birds

The unraveling of hormonal and sex chromosome control of sexual differentiation of the zebra finch Taeniopygia guttata brain has been particularly interesting. Male zebra finches sing a courtship song that females cannot sing, and the neural circuit for song is much larger in males [43]. When females are treated with estrogen at hatching, their song regions are permanently masculinized (larger) and they do sing 44, 45. This result suggests that, as in some mammals, the male brain is

Relevance to humans

In humans, the opportunities for detecting a sex chromosome effect on neural development are limited to studies of people with spontaneous deletions, translocations or duplications of sex chromosome genes. In many cases (e.g. XO, XXY or XYY) the unusual genetic constitution also influences gonadal secretions, making it difficult to disentangle sex chromosome and hormonal effects. However, XXY and XYY boys both have testes, but have recognizable social behavior phenotypes that are different from

Conclusions and future directions

If the sex chromosome constitution of brain cells contributes to sexual differentiation, how large might this effect be? Is the recent appreciation of this effect, decades after the divergence of the fields of sex determination and brain sexual differentiation in 1959, an indication that the role of the sex chromosomes is minor relative to the main masculinizing influence of testosterone? At present, the answers to these questions are not known. It is no accident that the first cases of sex

Acknowledgements

We thank Robin Lovell-Badge for comments on this manuscript and other discussions. This work was supported by NIH grants MH59268 and NS43196 to A.P.A.

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