Colciago A, Celotti F, Pravettoni A, Mornati O, Martini L, Negri-Cesi P
Department of Endocrinology, University of Milan, Via G. Balzaretti, 9, 20133, Milano, Italy.
Brain Res Dev Brain Res. 2005 Mar 31;155(2):107-16. doi: 10.1016/j.devbrainres.2004.12.003.
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 5 alpha-reduction of Testosterone to DHT, catalyzed by two 5 alpha-reductases (5 alpha-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 5 alpha-R1). It has been observed that, in both sexes, 5 alpha-R1 is significantly higher around birth than prenatally, and that 5 alpha-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 5 alpha-R2 and aromatase enzymes in a sex- and time-specific pattern.
在胎儿期大鼠下丘脑发生的通过芳香化酶将雄激素转化为雌激素的过程，导致了大脑的雄性特异性性别分化。芳香化酶在妊娠后期的有限时期内表现出表达和活性的峰值；然而，其在胚胎发育过程中表达的可能二态性尚不清楚。控制组织特异性芳香化酶表达的机制之一可能是转录变体的形成，这些变体在5'-非翻译区（5'-UTR）有所不同。外显子If是啮齿动物下丘脑-视前区使用的主要5'-UTR，也存在由不同外显子编码的少量其他变体。另一种可能参与大脑分化的酶促转化是睾酮经两种5α-还原酶（5α-R1型和2型）催化5α-还原为双氢睾酮。本研究的目的是通过半定量RT-PCR并行评估从妊娠第16天到出生后第5天（对于5α-R1仅到出生后第15天）的雄性和雌性大鼠中这三种酶的二态性特征以及大脑特异性芳香化酶的表达模式。已经观察到，在两性中，5α-R1在出生前后显著高于产前，并且5α-R2的表达在雄性中似乎高于雌性，特别是在出生后不久。此外，芳香化酶有两个表达峰值，这是雄性特异性的，分别在出生前和出生后；雄性仅使用外显子If，而雌性在出生后可能存在不同的转录本。得出的结论是，啮齿动物大脑的性别分化可能涉及5α-R2和芳香化酶两种酶以性别和时间特异性模式的激活。
