Activating signal cointegrator 1 is highly expressed in murine testicular Leydig cells and enhances the ligand-dependent transactivation of androgen receptor

Biol Reprod. 2002 Nov;67(5):1580-7. doi: 10.1095/biolreprod.102.006155.


Activating signal cointegrator 1 (ASC-1) has been recently reported as a coactivator of some nuclear receptors. In the present study, we have analyzed the expression of ASC-1 in the mouse testis and investigated its capacity to modulate the transcriptional activity of androgen receptor (AR). We found that although ASC-1 mRNA was ubiquitously expressed at a low level in mouse tissues, a couple of testis-specific mRNAs were expressed in the adult testis. Cloning of one testis-specific variant revealed that the ubiquitous and testis-specific transcripts of ASC-1 share at least the same open reading frame. The expression of the testis-specific ASC-1 mRNAs was developmentally regulated, and the onset of their expression coincided with the initiation of spermatogenesis. In situ hybridization of mouse testis with ASC-1 antisense probe demonstrated predominant expression of ASC-1 in the interstitial Leydig cells that express AR. Moreover, yeast two-hybrid tests and glutathione S-transferase pull-down assays revealed that ASC-1 associates directly with AR and that the hinge domain of AR and a putative zinc-finger motif of ASC-1 are major determinants for their interaction. Transient transfection assays performed by expressing ASC-1 in combination with AR and an androgen-responsive reporter gene showed that ASC-1 moderately alters the induction of the reporter gene. Taken together, these results suggest that ASC-1 may function as an AR coregulator and have a role in testicular functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cloning, Molecular
  • Humans
  • Leydig Cells / cytology
  • Leydig Cells / metabolism*
  • Ligands
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Organ Specificity
  • Protein Binding / physiology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Androgen / genetics*
  • Receptors, Androgen / metabolism
  • Sexual Maturation / physiology
  • Testis / cytology
  • Testis / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation*
  • Two-Hybrid System Techniques
  • Zinc Fingers


  • Ligands
  • RNA, Messenger
  • Receptors, Androgen
  • Transcription Factors
  • Trip4 protein, mouse