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Gonadal hormones profoundly influence brain physiology and behavior in vertebrates. During development, these hormones determine whether brains will function in a typically male or female fashion. In adulthood, environmentally induced, or endogenously programmed, changes in gonadal hormone levels alter hormone-sensitive functions or behaviors. These actions of gonadal hormones provide valuable tools in relating brain structure to function. In principle, one can relate sexual differentiation of hormone-sensitive functions with sexual differentiation of structures implicated in these functions. In addition, one can relate changes in structure and function that are induced by gonadal hormones in adult animals. The cellular and molecular mechanisms underlying these hormonal actions, however, are poorly understood.

Figure Legend: Vasopressin innervation (yellow dots) in the lateral septum of a female (left) and male rat (right).

Our lab addresses this issue by studying a sexually dimorphic group of forebrain neurons that produce the neuropeptide vasopressin. The projections of these neurons are much denser in males than in females. Gonadal hormones dramatically influence these neurons throughout life. For example, a drop in the level of sex hormones in adulthood is immediately followed by a reduction in vasopressin gene expression. It takes months, however, before vasopressin has disappeared from the terminals of these neurons. Such gradual changes may explain the gradual changes found in male sexual behavior and aggressive behavior after castration.

Research in the lab is centered around two main questions, How do males end up having many more vasopressin neurons than females, and What are the consequences of a sex difference in vasopressin innervation for brain function and behavior. Our research suggests that instead of influencing processes such as cell birth or cell death, testosterone permanently influences the neuropeptide expression in a fixed set of cells. How testosterone causes permanent changes in neuropeptide expression is the focus of our research. Interestingly, our research suggests that not only sex differences in gonadal hormone levels, but also the presence of a different set of sex chromosomes may directly contribute to the sexual differentiation of this system.

Figure Legend: Male (left) and female prairie vole (right) hovering over a pup (middle)

The answer to the second question is quite intriguing: sex differences in vasopressin innervation may cause as well as prevent sex differences in behavior. The latter can be illustrated with parental behavior in prairie voles. Female voles, like female rats, require the hormonal changes associated with pregnancy to be fully parental at the time pups are born. Male voles are equally parental towards their pups. As they don’t get pregnant, they must follow a different strategy. Our research suggests that this strategy involves the sexually dimorphic vasopressin innervation of the brain, which is active in male voles but appears insignificant in female voles. We study whether other sex difference may also play such a double role.

For more information, you could read for example:

De Vries GJ, Boyle PA. 1998. Double duty for sex differences in the brain. Behav. Brain Res. 92: 205-213.

De Vries GJ, Panzica GC. 2006 Sexual differentiation of central vasopressin and vasotocin systems in vertebrates: different mechanisms, similar endpoints.

De Vries GJ. 2004. Sex differences in adult and developing brains; compensation, compensation, compensation. Endocrinology, 145: 1063-1068.


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