THE NUCLEAR RECEPTOR STEROIDOGENIC FACTOR-1 ACTS AT MULTIPLE LEVELS OF THE REPRODUCTIVE AXIS
THE NUCLEAR RECEPTOR STEROIDOGENIC FACTOR-1 ACTS AT MULTIPLE LEVELS OF THE REPRODUCTIVE AXIS
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DOI：
10.1101/gad.8.19.2302
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发表时间：
1994-10-01
影响因子：
10.5
通讯作者：
PARKER, KL
中科院分区：
文献类型：
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作者：
INGRAHAM, HA;LALA, DS;PARKER, KL
类固醇生成因子1（SF-1）是一种孤儿核受体，调节产生性类固醇的酶，编码SF-1的Ftz-F1基因的破坏会阻止肾上腺和性腺的发育。我们现在研究SF-1在下丘脑/垂体/性腺轴其他水平的作用。在Ftz-F1破坏的小鼠中，抗垂体促激素抗体的免疫组织化学分析显示促性腺激素特异性标志物的选择性丢失，支持SF-1在促性腺激素功能中的作用。原位杂交分析证实了这些结果;来自Ftz-F1破坏小鼠的垂体缺乏三种促性腺激素特异性标志物（LH β、FSH β和促性腺激素释放激素受体）的转录物，而它们表现出糖蛋白激素α亚基的表达降低但可检测到。SF-1转录本在发育中的小鼠垂体中，在胚胎第13.5-14.5天首次可检测到，先于FSH β和LH β转录本的出现。在成年大鼠垂体细胞，SF-1成绩单共定位与促性腺激素特异性LH的免疫反应。最后，SF-1与糖蛋白激素α亚基基因中先前定义的启动子元件相互作用，为Ftz-F1破坏小鼠中促性腺激素表达受损提供了可能的机制。这些研究确立了这种孤儿核受体在生殖功能中的新作用。
Steroidogenic factor 1 (SF-1), an orphan nuclear receptor, regulates the enzymes that produce sex steroids, and disruption of the Ftz-F1 gene encoding SF-1 precludes adrenal and gonadal development. We now study the role of SF-1 at other levels of the hypothalamic/pituitary/gonadal axis. In Ftz-F1-disrupted mice, immunohistochemical analyses with antibodies against pituitary trophic hormones showed a selective loss of gonadotrope-specific markers, supporting the role of SF-1 in gonadotrope function. In situ hybridization analyses confirmed these results; pituitaries from Ftz-F1-disrupted mice lacked transcripts for three gonadotrope-specific markers (LH beta, FSH beta, and the receptor for gonadotropin-releasing hormone), whereas they exhibited decreased but detectable expression of the alpha-subunit of glycoprotein hormones. SF-1 transcripts in the developing mouse pituitary, which first became detectable at embryonic day 13.5-14.5, preceded the appearance of FSH beta and LH beta transcripts. In adult rat pituitary cells, SF-1 transcripts colocalized with immunoreactivity for the gonadotrope-specific LH. finally, SF-1 interacted with a previously defined promoter element in the glycoprotein hormone alpha-subunit gene, providing a possible mechanism for the impaired gonadotropin expression in Ftz-F1-disrupted mice. These studies establish novel roles of this orphan nuclear receptor in reproductive function.