Steroid receptor coactivator (SRC)-1 and SRC-3 differentially modulate tissue-specific activation functions of the progesterone receptor

被引：83

作者：

Han, SJ ^{[1
]}

DeMayo, FJ ^{[1
]}

Xu, JM ^{[1
]}

Tsai, SY ^{[1
]}

Tsai, MJ ^{[1
]}

O'Malley, BW ^{[1
]}

机构：

[1] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

来源：

MOLECULAR ENDOCRINOLOGY | 2006年 / 20卷 / 01期

关键词：

D O I：

10.1210/me.2005-0310

中图分类号：

R5 [内科学];

学科分类号：

1002 [临床医学]; 100201 [内科学];

摘要：

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.

引用

页码：45 / 55

页数：11

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