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Roles of steroid receptor coactivator (SRC)-1 and transcriptional intermediary factor (TIF) 2 in androgen receptor

Xiangcang Ye1, Sang Jun Han, Sophia Y Tsai

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

Proceedings of the National Academy of Sciences of the United States of America
|June 29, 2005
PubMed

Insights

Transcriptional intermediary factor 2 (TIF2) is the primary coactivator for androgen receptor (AR) in mouse testes. Steroid receptor coactivator 1 (SRC-1) does not rescue AR activity and may negatively regulate it.

Area of Science:

  • Molecular Endocrinology
  • Reproductive Biology
  • Genetics

Background:

  • Steroid receptor coactivators (SRCs) play crucial roles in nuclear receptor function.
  • SRC-1 and TIF2/SRC-2 are key coactivators with distinct roles.
  • The specific contribution of SRC-1 and TIF2 to androgen receptor (AR) transcriptional activity in vivo remains to be fully elucidated.

Purpose of the Study:

  • To quantify the cell-specific contributions of SRC-1 and TIF2 to AR transcriptional activity in the mouse testis.
  • To investigate the in vivo interactions between AR and its coregulators.

Main Methods:

  • Generation of unique transgenic AR-reporter mice (AR-luciferase and AR-lacZ).
  • Derivation of bigenic mice by crossing AR reporter mice with SRC-1-/- or TIF2+/- mutant mice.
  • Analysis using in vivo imaging, luciferase assays, and immunohistology.

Main Results:

  • Testicular AR activity was significantly decreased in TIF2+/- mice, but not in SRC-1+/- mice.
  • TIF2 was identified as the preferential coactivator for AR in the testis.
  • SRC-1 did not rescue AR activity in TIF2 mutant mice and appeared to negatively influence AR activity.

Conclusions:

  • TIF2 is the predominant coactivator for AR in mouse testicular Sertoli cells.
  • SRC-1 plays a distinct, potentially inhibitory, role in AR activity in the testis.
  • These findings offer novel in vivo insights into AR-coregulator interactions in a cell-type-specific manner.

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