During ontogeny hormones secreted by the fetal gonads determine how the brain develops. The secretion of the male hormone, testosterone, masculinizes the developing brain; in the absence of testosterone a feminine brain develops. As a consequence of the endocrine milieu during development, therefore, adult male and female brains are structurally and functionally different. In fact, the sex difference in the structure of the brain is directly related to sex differences in sexual behavior and sex differences in neuroendocrine control mechanisms that regulate reproduction. Sexual behavior is the most dramatic example of sexually dimorphic brain-behavior relations.

      Many behaviors and other neural functions are important for reproduction, in addition to those directly mediating copulation and gamete production. In my laboratory we have been investigating the mechanisms by which gonadal hormones, and the hormones estrogen in particular, can modulate neural activity and behaviors mediated by one particular area of the brain, the basal ganglia. The basal ganglia are a group of brain structures important for the initiation and control of sensory and motor functions. My research has shown that estrogen treatment in female rats enhances the activity of one type of neuron found in the basal ganglia and enhances behaviors thought to be mediated by the striatum, a subregion of the basal ganglia. Furthermore, the effects of estrogen in this regard are sexually dimorphic, in the male rat estrogen does not produce the same effects. Developing this idea further, my laboratory has been investigating how the enhancement of basal ganglia activity is important for reproduction in the female rat.

      Experiments from my laboratory have shown that there is enhanced release of the neurotransmitter dopamine in the striatum of female rats during sexual behavior, but only when the context of the mating sequence allows the female rats to initiate and terminate contacts with the male. This behavioral modulation of sexual behavior normally occurs in the wild, and enhances a female rat's fertility. Furthermore, estrogen acts in the striatum and nucleus accumbens of the female rat to differentially affect sensorimotor vs. motivational aspects of sexual behavior, respectively. Interestingly, the drug tamoxifen, which is an antagonist at the breast and uterine estrogen receptor, has no effect in the striatum.

      The mechanism through which estrogen influences striatal function to affect sexual behavior in the female rat appears to be sexually dimorphic. Experiments in my laboratory have shown that estrogen in the striaturm influences the activity of neurons that use the neurotransmitter dopamine, and also has post-synaptic effects on dopamine receptor function in the basal ganglia. Building on my research on this topic, which began over sixteen years ago, we have shown that there are sex differences in the basal extracellular concentration of dopamine in the striatum and in the rapid effect of a single injection of estrogen on the behavioral and neurochemical responses to drugs like amphetamine that induce dopamine release. There are also sex differences in the rapid and acute effects of estrogen on striatal dopamine receptor binding, that mirror the hormonal effects on striatal dopamine release.

     The fact that estrogen induces these rapid effects in the striatum brings out another important aspect of this research. Our data suggest that estrogen acts in the striatum with a neurotransmitter-like effect, which is quite different from the hormone effect it has in other areas of the brain. Experiments recently published demonstrate that estrogen can act in the striatum on membrane-associated receptors that are pharmacologically distinct from classical estrogen receptors found in the uterus and breast tissue.

     To summarize, there are two new ideas developed in this research. First, estrogen has rapid effects in the brain mediated by a novel receptor mechanism. Second, these rapid effects of estrogen influence the female's behavior during sexual interactions to behaviorally enhance fertility by enhancing sensorimotor function. These studies are important for basic neuroscience - we are learning more about the mechanisms mediating hormone - brain interactions, and the neural control of reproductive behavior. There are also important clinical implications, as these novel receptors for the reproductive hormones may have important functions in human behavior. For example, the effects of estrogen on the striatum enhance performance of female rats on a skilled tasks, and work by Hampsom and Kimura has found that women show enhanced skilled motor performance at times during the menstrual cycle when estrogen is elevated. So, as we learn more about how estrogen acts in the brain we may learn more about how it affects human behavior as well.