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

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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.