Gonadotropin gene modulation by steroids and gonadotropin-releasing hormone.
Gonadotropin gene modulation by steroids and gonadotropin-releasing hormone.
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DOI：
10.1095/biolreprod54.2.279
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发表时间：
1996-02
影响因子：
3.6
通讯作者：
M. Shupnik
中科院分区：
文献类型：
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作者：
M. Shupnik
生理性促性腺激素水平由性类固醇和下丘脑 GnRH 脉冲发生器之间复杂的相互关系调节，类固醇和 GnRH 分别调节促性腺激素亚基（α、LH β、FSH β）基因表达。类固醇可以直接作用于垂体水平或间接作用于下丘脑以改变 GnRH 脉冲，并且它们可以产生积极或消极的作用，具体取决于模型系统和生理状态。 GnRH 脉冲频率和幅度对促性腺激素基因具有亚基特异性影响，并且生殖周期期间脉冲频率的改变可以选择性地有利于 LH 或 FSH 合成。促性腺激素亚基基因的克隆和转录调控研究的敏感分子方法使我们能够深入了解类固醇和 GnRH 的作用位点以及此类激素效应发生的机制。本综述描述了几种此类方法，包括通过核径流测定测量内源基因转录、通过瞬时转染分析定义激素敏感基因区域，以及使用转基因动物技术来验证基因表达的激素和组织特异性控制。最近在大鼠模型中的研究表明，一些类固醇的作用，例如雌激素对 LH β 基因转录的刺激以及雌激素和 GnRH 受体数量的改变，直接发生在垂体水平，而雌激素对促性腺激素的抑制作用即使不是主要通过下丘脑作用，也至少部分发生。 GnRH 脉冲的变化也可能改变 GnRH 受体数量，从而改变促性腺激素接收的潜在信号。当前和新兴的分子技术可能会识别类固醇和 GnRH 作用的其他目标，并允许更深入地了解促性腺激素调节和生殖功能。
Physiological gonadotropin levels are modulated by complex interrelationships between the sex steroids and the hypothalamic GnRH pulse generator, and the steroids and GnRH individually regulate gonadotropin subunit (alpha, LH beta, FSH beta) gene expression. Steroids may act directly at the pituitary level or indirectly at the hypothalamus to alter GnRH pulses, and they can have positive or negative actions, depending on the model system and physiological state. GnRH pulse frequency and amplitude have subunit-specific effects on the gonadotropin genes, and alteration of pulse frequency during the reproductive cycle can selectively favor LH or FSH synthesis. The cloning of the gonadotropin subunit genes and sensitive molecular approaches to the study of transcriptional regulation have permitted insights into the sites of steroid and GnRH action and into the mechanisms by which such hormonal effects occur. This review describes several such approaches including the measurement of endogenous gene transcription by nuclear run-off assays, definition of hormone-sensitive gene regions by transient transfection analysis, and the use of transgenic animal technology to verify hormonal and tissue-specific control of gene expression. Recent studies in the rat model suggest that some steroid actions, such as estrogen stimulation of LH beta gene transcription and alteration of estrogen and GnRH receptor number, occur directly at the level of the pituitary, while suppressive effects of estrogen on gonadotropins may occur at least partly if not primarily via hypothalamic effects. Changes in GnRH pulses may also alter GnRH receptor number, thus modifying the potential signal received by the gonadotroph. Current and emerging molecular technologies will probably identify additional targets of steroid and GnRH action and allow greater insight into gonadotropin regulation and reproductive function.