Steroid receptor coactivator (SRC)-1 and SRC-3 differentially modulate tissue-specific activation functions of the progesterone receptor
Steroid receptor coactivator (SRC)-1 and SRC-3 differentially modulate tissue-specific activation functions of the progesterone receptor
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DOI：
10.1210/me.2005-0310
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发表时间：
2006-01-01
影响因子：
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通讯作者：
O'Malley, BW
中科院分区：
文献类型：
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作者：
Han, SJ;DeMayo, FJ;O'Malley, BW
孕激素受体（PR）及其辅激活子和辅抑制子在女性生殖功能中起重要作用。为了研究体内基因转录调控所需的PR和类固醇受体辅激活因子（SRC）之间的功能相互作用，我们将PR活性指示剂（PRAI）小鼠与SRC-1（（+/-））和SRC-3（（+/-））小鼠杂交，以产生双基因小鼠PRAI-SRC 1（（-/-））和PRAI-SRC-3（（-/-））。在乳腺中，野生型和SRC-1（（-/-））小鼠的腔上皮中的PR活性被雌激素+孕酮处理诱导。相比之下，接受相同治疗的SRC-3（（-/-））小鼠中未检测到腔上皮PR活性增加。在子宫中，野生型和SRC-3（（-/-））小鼠的间质区室中的PR活性由雌激素+孕酮处理诱导。SRC-1（-/-）小鼠PR活性无明显升高。两者合计，我们的数据表明，PR在不同的组织中的内源性生理功能是由不同的类固醇受体辅调节。SRC-3是乳腺中PR的主要共激活因子，SRC-1是子宫中PR的主要共激活因子。
The progesterone receptor ( PR) and its coactivators and corepressors play an important role in female reproductive function. To investigate the functional interactions between PR and steroid receptor coactivators ( SRCs) required for regulation of gene transcription in vivo, we crossed PR activity indicator ( PRAI) mice with SRC-1((+/-)) and SRC3-((+/-)) mice to generate bigenic mice, PRAI-SRC1((-/-)) and PRAI-SRC-3((-/-)). In the mammary gland, PR activity in the luminal epithelium of both wildtype and SRC-1((-/-)) mice was induced by estrogen + progesterone treatment. In contrast, an increase in PR activity in the luminal epithelium was not detected in SRC-3((-/-)) mice with the same treatment. In the uterus, PR activity in the stroma compartment of both wild-type and SRC-3((-/-)) mice was induced by estrogen + progesterone treatment. However, the increased PR activity was not detected in SRC-1((-/-)) mice. Taken together, our data indicate that the endogenous physiological function of PR in distinct tissues is modulated by different steroid receptor coregulators. SRC-3 is the primary coactivator for PR in breast and SRC-1 is the primary coactivator for PR in uterus.