HUMAN SEXUALITY: MORPHOLOGIC DIFFERENTIATION OF THE BRAIN
Fetal androgen programs not only the differentiation of the internal and external genitalia but also the differentiation of sex-related pathways in the brain. Exactly how androgen affects brain differentiation is not known. It is probable that it acts on neural substrates which in turn regulate thresholds for the expression of sexually dimorphic behavior. Cyclic secretion of gonadotropins is sexually dimorphic. Hormonally, females cycle and males do not. In female rats, the ventromedial and preoptic areas of the hypothalamus regulate the cyclic secretion of gonadotropins. If female rat fetuses or neonates receive androgen, then, in adulthood, they are acyclic.
Regarding sexual behavior on mating tests, prenatally androgen-treated female rats behave more like males than do untreated females. They also resemble control males on various dimorphic nonmating tests, including tests for some forms of aggressive behavior, wheel running, and open-field behavior. Exposure to androgen after the critical period does not produce these masculinizing effects.
The experimental opposite of fetal androgenization of the female is not estrogenization but deandrogenization by fetal castration or anti-androgenization of the male. Male rat pups castrated immediately after birth are cyclic, like females, in gonadotropin release. The use of antiandrogen (cyproterone acetate) is even more dramatic in its effect. When injected into the pregnant female at the critical period in fetal development, the fetal testes of the XY fetuses become dormant and fail to supply androgen to the primordia of the external genitalia. Consequently, these chromosomally male pups are born with completely normal-appearing female genitals. By castrating them to eliminate all further influence of their own androgenic hormone and by giving replacement doses of female hormone at puberty, it is possible to obtain female mating behavior from these treated males. The stud males of the colony do not distinguish them from normal females.
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