Estrogen regulation of GnRH neurons in male mice

性状（由申请方提供）：促性腺激素释放激素（GnRH）是驱动所有脊椎动物生殖功能的主要激素，是青春期开始所必需的。调节雄性哺乳动物青春期开始的因素知之甚少，但它是公认的性腺类固醇激素发挥了突出的作用。最近在GnRH神经元中发现的雌激素受体表明雌激素可能直接作用于GnRH神经元以调节其功能。本文提出的实验将确定：a）性成熟期间雌激素受体β（ER-β）及其剪接变体在雄性小鼠脑中的分布; B）雌激素是否在体内调节GnRH启动子活性以及这种调节是否在青春期发生变化;以及c）雌激素是否通过ER-β或其剪接变体在体外改变GnRH启动子活性。总的来说，这些研究将提供重要的信息机制调节雄性哺乳动物的青春期。

DESCRIPTION (provided by applicant): Gonadotropin-releasing hormone (GnRH) is the primary hormone driving all vertebrate reproductive function and is absolutely required for the initiation of pubertal onset. The factors regulating pubertal onset in male mammals are poorly understood, however it is well accepted that gonadal steroid hormones play a prominent role. The recent discovery of estrogen receptors in GnRH neurons suggests the likelihood that estrogen acts directly on the GnRH neuron to modulate its function. The experiments proposed herein will establish: a) the distribution of estrogen receptor beta (ER-beta) and its splice variants in the brain of male mice during sexual maturation; b) if estrogen modulates GnRH promoter activity in vivo and whether this regulation changes across puberty; and c) if estrogen alters GnRH promoter activity through ER-beta or its splice variants in vitro. Overall these studies will provide important information about the mechanisms regulating puberty in male mammals.