Partial hormone resistance in mice with disruption of the steroid receptor coactivator-1 (SRC-1) gene

J Xu1, Y Qiu, F J DeMayo

  • 1Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.

Science (New York, N.Y.)
|April 16, 1998
PubMed

Insights

Steroid receptor coactivator SRC-1 (steroid receptor coactivator-1) is crucial for steroid hormone responses in mice. Gene inactivation led to reduced organ development and partial hormone resistance, indicating SRC-1

Area of Science:

  • Molecular biology
  • Endocrinology
  • Genetics

Background:

  • Steroid receptor coactivators (SRCs) are critical for mediating the effects of steroid hormones.
  • SRC-1 is a key member of the SRC family, but its precise in vivo function remains incompletely understood.

Purpose of the Study:

  • To investigate the in vivo biological function of SRC-1.
  • To determine the consequences of SRC-1 gene inactivation on steroid hormone responses in mice.

Main Methods:

  • Gene targeting was used to create SRC-1 null mutant mice.
  • Phenotypic analysis of homozygous mutants, including assessment of reproductive organ development and response to steroid hormones.

Main Results:

  • Homozygous SRC-1 mutant mice were viable and fertile.
  • Target organs (uterus, prostate, testis, mammary gland) showed reduced growth and development in response to steroid hormones.
  • Expression of TIF2, a related coactivator, was upregulated in SRC-1 null mutants, suggesting partial compensation.

Conclusions:

  • SRC-1 plays a significant role in mediating steroid hormone responses in vivo.
  • Loss of SRC-1 function leads to partial resistance to steroid hormones and impaired development of hormone-responsive tissues.