Sex differences in the brain: The relation between structure and function

https://doi.org/10.1016/j.yhbeh.2009.03.012Get rights and content

Abstract

In the fifty years since the organizational hypothesis was proposed, many sex differences have been found in behavior as well as structure of the brain that depend on the organizational effects of gonadal hormones early in development. Remarkably, in most cases we do not understand how the two are related. This paper makes the case that overstating the magnitude or constancy of sex differences in behavior and too narrowly interpreting the functional consequences of structural differences are significant roadblocks in resolving this issue.

Section snippets

The structure–function relationship

The prediction in the Phoenix et al. (1959) paper that early androgen exposure causes “a more subtle change reflected in function rather than in visible structure” proved to be too cautious after the first reports on sex differences in the brain started to trickle in. For example, in 1960 Kato detected higher serotonin levels in female than in male rat brains (Kato, 1960). Not much later Pfaff (1966) showed that neonatal castration of rats permanently changed the size of nucleoli in the

Sex similarities

A recent study suggested that a single gene deletion can wipe out sex differences in male sexual behavior. Female mice that are deficient in Trpc2, an ion channel that is expressed in the epithelium of the vomeronasal organ (VNO) and probably functions in pheromone detection (Liman et al., 1999), showed high levels of male sexual behavior (Kimchi et al., 2007). The data suggest that VNO-mediated input represses male and activates female behavior and that functional neuronal circuits underlying

Sex differences in brain structure may cause as well as prevent sex differences in behavior

We now know that organizational effects impinge on neural structures and behaviors beyond those related to reproduction. Intuitively, we associate structural differences with differences in physiological and behavioral endpoints. If the latter do not differ, we typically do not search for differences in mechanisms. However, sex differences at one or another level in the mechanisms underlying any physiological or behavioral endpoint, sexually dimorphic or not, may be the norm, not the exception.

Epilogue

While the search for the “Organizing action of prenatally administered testosterone propionate on the tissues mediating mating behavior…” (Phoenix et al., 1959) remains elusive, selective genetic elimination or re-introduction of elements of sexually dimorphic neural systems may change the scene. To ensure success, however, we have to realize that sex differences in function and behavior are context-dependent; context can alter gene expression in the brain, and genes, of course, “… do not

Acknowledgments

Research by GJD is funded by NIH grant MH047538 and NSF grant IBN 9421658. We thank Elsevier for permission to reproduce Fig. 1.

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