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

确定下丘脑雌激素反应性性别二态性的基因的鉴定

• 批准号: 05454117
• 负责人: NISHIHARA Masugi
• 金额: $ 3.9万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454117/
• 关键词: Hypothalamus; Estrogen; Sex differentiation; Multiunit activity; Luteinizing hormone; Gonadotropin-releasing hormone; cDNA subtraction; Gene expression; DNAサブトラクション

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.

本研究通过电生理方法阐明了性腺类固醇雌激素作用的脑区，并通过减cDNA方法阐明了雌激素激活表达的基因。使用从新生或成年切除卵巢的雌性大鼠下丘脑提取的mrna，进行cDNA减法。在新生大鼠下丘脑中分离了52个克隆作为雌激素应答基因。对部分克隆进行了测序，发现其中含有一种细胞生长因子基因。此外，该基因的表达在下丘脑腹内侧核中被证明是相当有限的。这个基因可能在这个阶段大脑的性别分化中起着重要的作用。另一方面，从成年大鼠中分离出32个克隆。其中一种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两个基因参与雌激素对大脑的作用。我们现在正在研究这些基因产物的功能。

项目成果

Hirasawa M,et al.: "The rostral ventrolateral medulla mediates suppression of the circulatory system by the ventromedial nucleus of the hypothalamus" Brain Research. (in press).

Hirasawa M,et al.：“延髓头侧腹外侧介导下丘脑腹内侧核对循环系统的抑制”大脑研究。

Nishimura F,et al.: "Changes in chemical sensitivity of rat ventromedial hypothalamic neurons by food deprivation" Physiology & Behavior. (in press).

Nishimura F 等人：“食物剥夺导致大鼠腹内侧下丘脑神经元化学敏感性的变化”

Nishihara M,Sano A,他: "Cessation of the electrical activity of gonadropin-releasing hormone pulse generator during the steroid-induced surge of luteinizing hormone in the rat" Neuroendocrinology. 51. 513-519 (1994)

Nishihara M、Sano A 等人：“在类固醇诱导的大鼠黄体生成激素激增期间，促性腺激素释放激素脉冲发生器的电活动停止”《神经内分泌学》51. 513-519 (1994)。

K.Narita,T.Yokawa,M.Nishihara,M.Takahashi: "Interaction between Excitatory and Inhibitory Amino Acids in the Ventromedial Nucleus of the Hypothalamus in Inducing Hyper-Running." Brain Research. 603. 243-247 (1993)

K.Narita，T.Yokawa，M.Nishihara，M.Takahashi：“下丘脑腹内侧核中兴奋性和抑制性氨基酸之间的相互作用诱导超跑。”

R-Z.Lu,S.Matsuyama,M.Nishihara,M.Takahashi: "Developmental Expression of Activin/Inhibin βA,βB and α Subunits,and Activin receptor-IIB Genes in Preimplantation Mouse Embryos." Biology of Reproduction. 49. 1163-1169 (1993)

R-Z.Lu、S.Matsuyama、M.Nishihara、M.Takahashi：“激活素/抑制素 βA、βB 和 α 亚基以及激活素受体-IIB 基因在植入前小鼠胚胎中的发育表达。49。1163-” 1169 (1993)