Expression of androgen-activating enzymes in cultured cells of developing rat brain

Abstract

Dihydrotestosterone and estradiol, two active metabolites formed locally in the brain from testosterone, modulate several functions of the developing rat CNS; these compounds derive from the 5α-reduction or the aromatization of the A-ring of the hormone. Also, progesterone and corticosteroids may be 5α-reduced and subsequently 3α-hydroxylated, becoming modulators of specific neuronal functions. Although the aromatase is a single enzyme, two types of 5α-reductase have been cloned, showing peculiar biochemical properties and probably different functions. Therefore, the isoform(s) of the enzyme 5α-reductase(s) present in early stage of brain development have been characterized in primary neuronal and glial cell cultures obtained from the fetal or neonatal rat brain, respectively. Aromatase expression was also studied. The results have shown that in all the brain cells examined type 1 5α-reductase mRNA is expressed. No specific transcript of type 2 5α- reductase is detectable in any of the cell types examined. Finally, the aromatase gene is expressed only in cultured fetal neurons and especially in those derived from the hypothalamic area of the rat embryos. It is interesting that no aromatase mRNA is detectable in mixed gila or in type 1 astrocytes and oligodendrocytes cultured separately.