Estrogen regulation of GnRH neurons in male mice

描述（申请人提供）：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，是青春期开始的绝对必需激素。调节雄性哺乳动物青春期发生的因素尚不清楚，但性腺类固醇激素在其中起着重要作用已被广泛接受。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。本实验拟建立：a)雄性小鼠性成熟过程中雌激素受体β (er - β)及其剪接变异体在大脑中的分布；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；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，这些研究将为雄性哺乳动物青春期的调节机制提供重要信息。

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.