Steroid receptor coactivator (SRC)-1 and SRC-3 differentially modulate tissue-specific activation functions of the progesterone receptor.
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 SRC-3(+/-) mice to generate bigenic mice, PRAI-SRC-1(-/-) and PRAI-SRC-3(-/-). In the mammary gland, PR activity in the luminal epithelium of both wild-type 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.
Han
Sang Jun
SJ
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
DeMayo
Francesco J
FJ
Xu
Jianming
J
Tsai
Sophia Y
SY
Tsai
Ming-Jer
MJ
O'Malley
Bert W
BW
D000818:Animals; D003433:Crosses, Genetic; D004967:Estrogens / Q000494:pharmacology / Q000502:physiology; D005260:Female; D051548:Histone Acetyltransferases; D008321:Mammary Glands, Animal / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3; D011374:Progesterone / Q000494:pharmacology / Q000502:physiology; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014599:Uterus / Q000378:metabolism*
D004967:Estrogens; D011980:Receptors, Progesterone; D015534:Trans-Activators; D014157:Transcription Factors; D011374:Progesterone; D051548:Histone Acetyltransferases; C538861:Ncoa1 protein, mouse; C538867:Ncoa3 protein, mouse; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3