Mechanism of brain sexual differentiation by regulation of aromatase and sex-steroid receptors.

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The presence of neuronal aromatase has been immunohistochemically determined in the aldehyde-fixed rat and monkey brains. The most striking aromatase-immunoreactive (AROM-I) neurons are present in the medial preoptico-amygdaloid neuronal arcs (mPOAM arcs) in both animals. The regions have been considered as centers of reproductive functions and larger in size in males than in females, confirming that intracranial estrogen-biosynthesis is essential to development of reproductive neural substrates and functions in mammals. They appear by E15 in the rat, reaching a peak in staining intensity between El 8-P2 and diminishing after the perinatal stage. Expression in the mPOAM arc are clearly more prominent in males in number and immunoreactivity than in females, especially after young-to-adult stages. The AROM-I neurons have also been clarified to show sexually dimorphic expression for both alpha-estrogen and androgen receptors (EsR and AnR). In neonates, expression of EsR in the mPOAM arc i … More s already more prominent in females than in males, whereas that of AnR is more prominent in males than in female. In young-to-adult stages, the sexually dimorphic expressions are further enhanced in accordance with increased expressions of EsR in females or AnR in males during adolescence. Neonatal castration in male rats was found to change the male's pattern to the female's one with respect to AROM, EsR and AnR in the mPOAM arc. Administration of 5alpha-dihydrotestosterone strongly increases the expressions of AROM and AnR and slightly increase EsR, while 17beta-estradiol slightly increases the expressions of AROM and AnR and strongly decreases the expression of EsR.Testosterone strongly increases the expressions of AROM and AnR, and strongly decreases the expression of EsR in the mPOAM arc, indicating that only testosterone can recovered expression of the male pattern in the neonatally castrated male rats. Thus, some testosterones are considered to be actually aromatized into estradiol and to down-regulate EsR, while others sparing aromatization can act directly on AnR in the mPOAM arc. A complete male probably requires not only masculinization by enhancement of an AnR-stimulation via the up-regulation of AnR but also defeminization by reduction of an EsR-stimulation via the down-regulation of EsR in the Iimbic arc. Less