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Abstract: Aromatase (P450AROM), the enzyme responsible for the conversion of testosterone (T) into 17-β estradiol (E2), plays a crucial role in the sexual differentiation of specific hypothalamic nuclei. Moreover, recent findings indicate that local E2 synthesis has an impact on other brain areas including hippocampus, temporal cortex and cerebellum, and may thus influence also cognitive functions. Numerous studies have described the expression and the distribution of P450AROM throughout ontogenesis and postnatal development of the central nervous system in several mammals, but data referring to humans are scarce. In the adult human brain, P450AROM has been detected in the hypothalamus, limbic areas, and in the basal forebrain, and described in glial cells of the cerebral cortex and hippocampus. In this study we report the expression, distribution and cellular localization of P450AROM in the human fetal and early postnatal cerebral cortex. In our series of fetal brains of the second trimester, P450AROM expression appeared at gestational week (GW) 17 and resulted limited to groups of cells localized close to the growing neuroepithelium in the ventricular and subventricular zones. At GWs 20–24, scattered P450AROM immunoreactive (-ir) neural cells were identified in the intermediate plate and subplate, and in the parietal cortical plate. In perinatal and early postnatal individuals the quantity of P450AROM-ir elements increased, and revealed the morphology typical of glial cells. Double labeling immunostaining with anti-GFAP and anti-P450AROM antisera, and subsequent confocal analysis, confirmed this observation. Our data show that the expression of P450AROM in the fetal cortex starts approx at the end of the fourth gestational month, but increases steadily only in the last trimester or in the early postnatal period. This temporal trend may suggest that P450AROM could act as a differentiation-promoting factor, based on timing of the steroid actions. [Copyright &y& Elsevier]

Metallothioneins (MT) belong to a widespread family of proteins characterized by a high metal content (mainly Cu(2+) and Zn(2+)) and by the presence of cysteine residues. The expression of metallothionein I-II (MT I/II), glial fibrillary acid protein (GFAP), and vimentin was examined in a series of 16 developing human brains of the second trimester. The brains of a stillborn/newborn individual and two postnatal individuals were studied for comparison. MT I/II-containing cells became consistently and clearly visible only from gestational week 21 onwards. On the other hand, several densely packed GFAP- and vimentin-containing elements were evident in the neuroepithelium at several periventricular locations and in the subventricular zone of all fetuses of the series. GFAP- and vimentin-containing elements also entered the intermediate plate, but only a few elements were evident in the outer layers of the maturing cortex. The relatively late onset of MT I/II expression and their distribution are discussed in relation to the uptake of trace elements during the last trimester of pregnancy, and the role of astrocytes in neuronal guidance and maturation of cortical circuits.