Most people have a clear idea about how men and women are different. Most obvious differences, are related to the way we are build and the way we behave from birth. For example, newly born girls are more sensitive to touch, noise, pain, verbal emotion and discomfort than boys. Boys are more active and occupy more space on the playground. The infant sexual segregation "picks" by the age of four when boys and girls usually start to play apart. With age this attitude changes but behavioral differences only become more apparent and numerous. For example, ever intriguing differences in sexual behavior, play and social behavior, learning and gender role behavior, posture during urination, scent-marking behavior, vocalization, food and water intake. It is only reasonable to assume that behavioral differences are consistent with differences in organization and function of the relevant brain circuitry.

We know that male and female brains are different. Structural difference between the male and the female brain - sexual dimorphism - has been long detected morphologically in numerous brain structures including cell groups in the area critical to most hormonal, vegetative, emotional and reproductive responses in our behaviour - the hypothalamus, and other deep brain structures. Recent neuroimaging studies in the living brain identified sex differences in brain activity in various areas of the brain. Some of these areas are associated with language which in males appears to be highly lateralized in the lower left part of the frontal cortex, while in females the active areas are diffused between left and right parts of the lower frontal cortex. Differences also exist in relation to diseased states of the brain function. For example, prevalence of major depression is twice as high in females. Women are also more prevalent to anxiety, eating disorders, epilepsy, Alzheimer's disease and attempted suicide. Males are more susceptible to alcoholism and other drug abuse, antisocial behavior, attention deficit disorder, Tourette's syndrome and complete suicide. Relationship of gender to the etiology of these disease is unclear.

Another question is how do sex differences and sexual orientation develop? Experimental alteration of sex hormones concentration during development alters sexual behavior. Exposing females to androgen just before birth and blocking testosterone in males influences behavioral sex differences and differentiation of genitalia. Remarkably, female rats exposed to exogenous androgens during perinatal period develop a masculine peripheral and brain characteristics. Deprived of androgen, young male monkeys, for example, spend more time with their mothers then their piers who also display seven times the blood concentration of testosterone. It is now thought that it is predominantly testosterone that determines the masculine morphology of the brain at the early stages of development. Lack of testosterone determines a feminine brain. Any environmental aspect that may influence secretion of testosterone in early development could also influence the brain differentiation process. For example maternal stress has been shown to result in more feminine morphology of male rats brains.

Sexual dimorphism of many brain structures is most likely related to general differences in regulation of life support, behavior and physical characteristics, in others it is more relevant to the actual sexual behavior. For example, lower spinal cord contains a group of motoneurons that controls muscles of the penis. Unsurprisingly, this cell group in is more developed in males then in females. Sexual dimorphism of hypothalamic structures is particularly interesting because some hypothalamic cell groups are directly involved in the regulation of sexual behavior.

Many scientists now believe that the central regulation of sexual behavior is associated with a small, smaller than a thumb-nail, area in the hypothalamus which is called the medial preoptic nucleus (MPO). Experiments in animals revealed that the control of the sexual behavior is largely governed by interactions between sex steroid hormones in the MPO and other hypothalamic structures. For example, the sequential action of female sex hormones estradiol and progesterone in the MPO is a critical element of a stereotypic female rat reproductive behavior - lordosis. Administration of a small amount of these steroids to the MPO will immediately activate female copulatory behavior. The MPO is also implicated in the regulation of the masculine sexual behavior. For example castration diminishes male copulatory behavior, but small amount of testosterone (chemical precursor of estradiol) injected into MPO will restore the lost capability. It appears, at least in primates, that testosterone directly activates male sexual behavior by binding to the androgen receptors in the MPO. Considering this general functional information it is apparent that the search for the neural centers controlling our sexual behavior should focus on MPO, but MPO is a complex structure comprised of several smaller cell groups.

Early histological studies in the rat brain identified a cell group in the center of the MPO that is 5 times bigger in males than in females. This important finding exposed a potential for depicting a triggering control center for sexual behavior in our brain. Because of the small size, the physiological and functional studies of this cell group were scarce. In fact it is still unclear what is the nature of the incoming and outgoing projections for this specific subnucleus. Nevertheless, the sexual dimorphism of this specific MPO subnucleus in the rat instigated efforts to establish human homologues to the subnuclei of the rat MPO, where the association of structures with connections and sexual behavior is better studied. These initial efforts were confined to simple histological methodology and capitalized on demonstrating sexual dimorphism of several small cell groups in the human medial preoptic area. The human homologue of the rat MPO, however, remained an enigma, which hindered the correlation of the sexually dimorphic cell groups in the human to subnuclei of the rat MPO. In fact, a short history of the human homologue of the MPO is tangled in contradiction and controversy. Firstly, Brockhaus in 1942 identified a small group of large cells in the rostral hypothalamus and referred to it as intermediate nucleus. Two decades ago, a well published discovery revealed that this cell group is sexually dimorphic - twice the size in adult men then in women. To emphasize the importance of the finding the cell group became referred to simply as the sexually dimorphic nucleus (SDN). The consensus was short lived though, and another, subsequent study disputed the sexual dimorphism of the SDN and for some reason renamed it, rather inelegantly to our opinion, into the interstitial nucleus of the anterior hypothalamus number 1. The controversy of the human sexual behavior control center deepened as the same study also identified three other small cell groups in and around MPO of which two were found to be sexually dimorphic. Concurrently, a separate study also found a small part of MPO to be almost double the size in heterosexual men compared to homosexual men. Most of the confusion may have been due to hitherto ill defined boundaries of MPO as well as from poor understanding of the structural compartmental organisation of the nucleus itself. The controversy has only been resolved recently with a study depicting a comprehensive structural organization of the human MPO including its sexually dimorphic subnuclei (Figure 1).

Because of uncertainty about the functional significance of sexual dimorphism in the brain, views on why it develops vary. For example, common lore tells us that sex differences in the brain cause sex differences in behavior. There is also, however, a possibility that sex differences in the brain may also do the exact opposite. Specifically, sex differences may allow males and females to display remarkably similar behaviors, despite major differences in their physiological and hormonal conditions. In other words, the obvious morphological differences may be a result of a compensatory mechanism adjusting for homeostatic differences between males and females. Morphologically, in the developing human the sexually dimorphic nucleus (In) of the MPO has been first identified at 16 weeks of development and it is thought that it develops evenly in males and females up until 2 years of age after which many cells of the female, but not male In, die to give the MPO sexual dimorphism. This information may help to determine the critical time for differentiation of our sexual behavior.

In conclusion, the sexual dimorphism between male and female brain includes structures directly involved in regulation of sexual behavior including the medial preoptic hypothalamic nucleus. The mechanism of sexual differentiation of the brain and MPO is most likely based on hormonal interactions during crucial period of fetal and postnatal development. Structural appreciation of MPO will now allow a specific application of the modern functional imaging technology which, in turn, may tell us more about the functional characteristic of the nucleus.

Figure 1. Schematic drawing shows the organisation and a relative location in the human brain of the medial preoptic nucleus - critical structure in the central regulation of sexual behavior. Two constituent parts of the MPO - the InM and the Un - are larger in men then in women.