The steroid receptor coactivator SRC-3 (p/CIP/RAC3/AIB1/ACTR/TRAM-1) is required for normal growth, puberty, female reproductive function, and mammary gland development.
Steroid receptor coactivator-3 (SRC-3) is a coactivator of nuclear receptors in the SRC family as assayed in vitro. Here, we show that mouse SRC-3 is expressed in a tissue-specific fashion and distributed mainly in the oocytes, mammary glands, hippocampus, olfactory bulb, smooth muscle, hepatocytes, and vaginal epithelium. Genetic disruption of SRC-3 in mice results in a pleiotropic phenotype showing dwarfism, delayed puberty, reduced female reproductive function, and blunted mammary gland development. Hormonal analysis indicates that SRC-3 plays a role in both the growth hormone regulatory pathway and the production of estrogen, which may explain the observed phenotypes. These results suggest that the physiological role of SRC-3 is different from that of SRC-1 and prove the diversity among coactivator family members.
Xu
J
J
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. jxu@bcm.tmc.edu
Liao
L
L
Ning
G
G
Yoshida-Komiya
H
H
Deng
C
C
O'Malley
B W
BW
D000818:Animals; D004958:Estradiol / Q000097:blood; D005260:Female; D006128:Growth; D051548:Histone Acetyltransferases; D008321:Mammary Glands, Animal / Q000502:physiology*; D051379:Mice; D056921:Nuclear Receptor Coactivator 3; D009928:Organ Specificity; D012098:Reproduction; D012741:Sexual Maturation; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D015534:Trans-Activators; D004958:Estradiol; D051548:Histone Acetyltransferases; C538867:Ncoa3 protein, mouse; D056921:Nuclear Receptor Coactivator 3