Normal reproductive function in mammals requires precise control of LH synthesis and secretion by gonadotropes of the anterior pituitary. Synthesis of LH requires expression of two genes [alpha-glycoprotein subunit (alphaGSU) and LHbeta] located on different chromosomes. Hormones from the hypothalamus and gonads modulate transcription of both genes as well as secretion of the biologically active LH heterodimer. In males and females, the transcriptional tone of the genes encoding alphaGSU and LHbeta reflects dynamic integration of a positive signal provided by GnRH from hypothalamic neurons and negative signals emanating from gonadal steroids. Although alphaGSU and LHbeta genes respond transcriptionally in the same manner to changes in hormonal input, different combinations of regulatory elements orchestrate their response. These hormone-responsive regulatory elements are also integral members of much larger combinatorial codes responsible for targeting expression of alphaGSU and LHbeta genes to gonadotropes. In this review, we will profile the genomic landscape of the promoter-regulatory region of both genes, depicting elements and factors that contribute to gonadotrope-specific expression and hormonal regulation. Within this context, we will highlight the different combinatorial codes that control transcriptional responses, particularly those that mediate the opposing effects of GnRH and one of the sex steroids, androgens. We will use this framework to suggest that GnRH and androgens attain the same transcriptional endpoint through combinatorial codes unique to alphaGSU and LHbeta. This parallelism permits the dynamic and coordinate regulation of two genes that encode a single hormone.

中文翻译：

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多种和重叠的组合代码协调激素的响应能力，并决定编码黄体生成素的基因的细胞特异性表达。

哺乳动物的正常生殖功能需要通过垂体前叶的促性腺激素精确控制LH的合成和分泌。LH的合成需要表达位于不同染色体上的两个基因[α-糖蛋白亚基（alphaGSU）和LHbeta]。下丘脑和性腺的激素调节两个基因的转录以及具有生物活性的LH异二聚体的分泌。在男性和女性中，编码alphaGSU和LHbeta的基因的转录音调反映了下丘脑神经元GnRH提供的正信号和性腺类固醇产生的负信号的动态整合。尽管alphaGSU和LHbeta基因以相同的方式对激素输入的变化做出转录反应，但调节元件的不同组合可协调其反应。这些激素反应性调节元件也是更大的组合代码的组成部分，这些组合代码负责将alphaGSU和LHbeta基因的表达靶向促性腺激素。在这篇综述中，我们将剖析这两个基因的启动子调节区域的基因组格局，描绘有助于促性腺激素特异性表达和激素调节的元素和因子。在这种情况下，我们将重点介绍控制转录反应的不同组合代码，尤其是那些介导GnRH和一种性类固醇雄激素的相反作用的组合代码。我们将使用该框架来建议GnRH和雄激素通过alphaGSU和LHbeta特有的组合代码获得相同的转录终点。