Dimorphic expression of testosterone metabolizing enzymes in the hypothalamic area of developing rats

Abstract

Androgen transformation into estrogens through the aromatase enzyme, occurring in the rat hypothalamus during fetal life, leads to male-specific sexual differentiation of brain. Aromatase shows a peak of expression and activity in a limited period during late gestation; however, the possible dimorphism in its expression during embryogenesis is unclear. One of the mechanisms controlling tissue-specific aromatase expression might be the formation of transcript variants, that differ in the 5′-untranslated regions (5′-UTR). Exon If is the major 5′-UTR used in rodent hypothalamic–preoptic area, with low amounts of other variants encoded by different exons I also present. Another enzymatic conversion, possibly involved in brain differentiation, is the 5alpha-reduction of Testosterone to DHT, catalyzed by two 5alpha-reductases (5alpha-R type1 and 2). Aim of the present study is to evaluate, in parallel, by semiquantitative RT-PCR, the dimorphic profile of the three enzymes and the pattern of the brain-specific aromatase expression in male and female rats from gestation-day 16 to postnatal-day 5 (or 15 only for 5alpha-R1). It has been observed that, in both sexes, 5alpha-R1 is significantly higher around birth than prenatally, and that 5alpha-R2 expression appears to be higher in males than in females, particularly just after birth. Moreover, aromatase has two expression peaks, that are male-specific, before and after birth; only exon If is used in males, while different transcripts might be present in females postnatally. It is concluded that rodent brain sexual differentiation probably involves the activation of both 5alpha-R2 and aromatase enzymes in a sex- and time-specific pattern.