La differenziazione sessuale del cervello: dall'animale sperimentale all'uomo

It is well known that several physiological and behavioral responses are gender-specific. These dimorphic responses are the result of both genetic and hormonal signals that cooperate in the development of some plastic brain structures toward sex-specific morphology and functions, during a critical period of the prenatal/early postnatal life. Circulating levels of testosterone (T), which arises from the differentiation of the gonads into testes, represent the main difference between the two sexes before birth. In males, T exhibits two peaks of secretion, one in the late gestation and the second in the early postnatal period, which are absent in females. In the process of brain sexual differentiation, T does not act in its native form, but needs to be converted into “active” metabolites through the action of specific enzymes. This paper will summarize the most important results obtained in our and other laboratories concerning the dimorphic pattern of expression of the two main enzymatic pathways that convert T into active metabolites within the rodent brain (5apha-reduction and aromatization) and the role of T metabolites in the sexual differentiation of the CNS. Some experimental models demonstrating the genetic influence on this process will also be described. In the last part of the paper some considerations on the influence of T metabolites in the sexual differentiation of the human brain, as well as on the possible biological basis of homosexuality and transexualism will be drawn.