Partial hormone resistance in mice with disruption of the steroid receptor coactivator-1 (SRC-1) gene.
The in vivo biological function of a steroid receptor coactivator was assessed in mice in which the SRC-1 gene was inactivated by gene targeting. Although in both sexes the homozygous mutants were viable and fertile, target organs such as uterus, prostate, testis, and mammary gland exhibited decreased growth and development in response to steroid hormones. Expression of RNA encoding TIF2, a member of the SRC-1 family, was increased in the SRC-1 null mutant, perhaps compensating partially for the loss of SRC-1 function in target tissues. The results indicate that SRC-1 mediates steroid hormone responses in vivo and that loss of its coactivator function results in partial resistance to hormone.
Xu
J
J
Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Qiu
Y
Y
DeMayo
F J
FJ
Tsai
S Y
SY
Tsai
M J
MJ
O'Malley
B W
BW
D000818:Animals; D002460:Cell Line; D004351:Drug Resistance; D004958:Estradiol / Q000097:blood / Q000494:pharmacology; D005260:Female; D018390:Gene Targeting; D005837:Genitalia, Male / Q000187:drug effects / Q000254:growth & development*; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D051548:Histone Acetyltransferases; D008297:Male; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000254:growth & development*; D051379:Mice; D056920:Nuclear Receptor Coactivator 1; D051958:Nuclear Receptor Coactivator 2; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011374:Progesterone / Q000097:blood / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects / Q000254:growth & development; D013234:Stem Cells; D013737:Testis / Q000187:drug effects / Q000254:growth & development; D013739:Testosterone / Q000097:blood / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014599:Uterus / Q000187:drug effects / Q000254:growth & development*
D012739:Gonadal Steroid Hormones; C498002:Ncoa2 protein, mouse; D051958:Nuclear Receptor Coactivator 2; D014157:Transcription Factors; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D051548:Histone Acetyltransferases; C538861:Ncoa1 protein, mouse; D056920:Nuclear Receptor Coactivator 1