Identification of genes determining sexual dimorphism in estrogen-responsiveness of the hypothalamus

本研究旨在通过电生理学方法阐明性腺激素雌激素作用的脑区，并通过消减cDNA方法阐明雌激素激活其表达的基因。以去卵巢或去卵巢的新生或成年雌性大鼠的下丘脑中提取的mRNAs为模板，进行基因消减。在新生大鼠下丘脑中分离到52个雌激素反应基因克隆。对部分克隆进行了测序，发现其中包含一种细胞生长因子基因。此外，该基因在下丘脑腹内侧核的表达也受到相当程度的限制。在这个阶段，这个基因可能在大脑的性别分化中起着重要的作用。另一方面，在成年大鼠体内分离到32个克隆。其中一个基因被发现是转录因子基因的同源物，可能与诱导促性腺激素激增和性行为有关。因此，我们可以成功地鉴定出两个与大脑中雌激素作用有关的基因。我们现在正在研究这些基因产物的功能。

This study was performed to elucidate brain regions where gonadal steroid estrogen acts by electrophysiological method, and also to elucidate genes of which expression was activated by estrogen by means of subtracted cDNA method. Using mRNAs extracted from the hypothalamus of either neonatal or adult ovariectomized female rats with or without estrogen treatment, cDNA subtraction was carried out. In the hypothalamus of neonatal rats, 52 clones were isolated as estrogen-responsive genes. A part of clones were sequenced and revealed to include a gene of a kind of cellular growth factors. Further, expression of this gene was shown to be rather restricted in the ventromedial nucleus of the hypothalamus. This gene probably plays an important role in sexual differentiaton of the brain at this phase. On the other hand, 32 clones were isolated in adult rats. One of which was found to be a homologue of a gene of a transcription factor, and might be involved in inducing gonadotropin surge and sex behavior. Thus, we could succeeded in identification of two genes involved in estrogen actions on the brain. We are now investigating the function of the products of these genes.