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

Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6379-84. doi: 10.1073/pnas.120166297.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Estradiol / blood
  • Female
  • Growth*
  • Histone Acetyltransferases
  • Mammary Glands, Animal / physiology*
  • Mice
  • Nuclear Receptor Coactivator 3
  • Organ Specificity
  • Reproduction*
  • Sexual Maturation*
  • Trans-Activators / deficiency
  • Trans-Activators / genetics
  • Trans-Activators / physiology*


  • Trans-Activators
  • Estradiol
  • Histone Acetyltransferases
  • Ncoa3 protein, mouse
  • Nuclear Receptor Coactivator 3