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Gene Review

Ncoa1  -  nuclear receptor coactivator 1

Rattus norvegicus

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Disease relevance of Ncoa1_predicted

  • We tested whether steroid receptor coactivator-1 (SRC-1) and nuclear corepressor (N-CoR) expression is altered by hypothyroidism in rat brains on gestational day 16 and postnatal day 15 [1].

High impact information on Ncoa1_predicted

  • We report that reducing SRC-1 protein interferes with the defeminizing actions of estrogen in neonatal rat brain [2].
  • Our data indicate that SRC-1 protein expression is critically involved in the hormone-dependent development of normal male reproductive behavior and brain morphology [2].
  • Treatment of animals with estrogen induced PR expression in the ERalpha-expressing mammary epithelial cells in the absence of detectable SRC-1 and did not affect the segregated pattern of SRC-1 and ERalpha expression [3].
  • Steroid receptor coactivator-1 (SRC-1) family members interact with steroid receptors, including estrogen receptor alpha (ERalpha) and progesterone receptor (PR), to enhance ligand-dependent transcription [3].
  • However, the expression of ERalpha and SRC-1 was found to be segregated in distinct subsets of cells within the epithelium of the estrogen-responsive rat mammary gland [3].

Biological context of Ncoa1_predicted

  • These observations indicate that DNA-induced, as well as ligand-induced, conformational change(s) of TR may influence the nature of its binding to SRC-1, and that the two NBDs of SRC-1 may play different roles to regulate ligand-dependent transactivation of TRs [4].
  • In addition, a natural isoform of SRC-1, SRC-1E, which lacks NBD-2, preserved TR as well as progesterone receptor-mediated coactivator function on reporter gene expression [4].
  • Because TERP-1 contains a dimerization domain and part of the coactivator binding pocket, we hypothesized that it modulates ER function by direct interactions with full-length ER or the steroid receptor coactivator, SRC-1 [5].
  • However, TERP-1 may compete with ER for binding sites of receptor cofactors because steroid receptor coactivator-1 (SRC-1) rescued the inhibitory actions of TERP-1 [6].
  • Furthermore, we found that SRC-1 and CBP function in brain to modulate the expression of hormone-dependent female sexual behavior [7].

Anatomical context of Ncoa1_predicted


Associations of Ncoa1_predicted with chemical compounds

  • In this study, the distribution of steroid receptor co-activator-1 (SRC-1) was examined with immunocytochemistry, in the lumbosacral cord of Wistar rats of both sexes [9].
  • Next, we similarly examined expression changes of ER alpha and beta, PR, and SRC-1 in animals exposed to MXC at 24, 240, and 1200 ppm, DINP at 4000 and 20,000 ppm, and GEN at 1000 ppm [11].
  • Thyroid hormone exerts site-specific effects on SRC-1 and NCoR expression selectively in the neonatal rat brain [1].
  • We found that both SRC-1 and N-CoR mRNA levels were decreased in the cortex and dentate gyrus of 6-n-propyl-2 thiouracil treated rats only on P15, while mRNA levels for both genes were increased in the same CA3 region of the brains [1].
  • Reduction of SRC-1 and CBP protein in brain disrupted ER-mediated activation of the behaviorally relevant progestin receptor gene [7].

Other interactions of Ncoa1_predicted

  • Such coactivators include three members of the 160 kDa proteins (p160s): SRC-1, TIF2/GRIP1, and p/CIP/RAC3/ACTR/AIB1/TRAM-1 [8].
  • PR was neither expressed nor induced by estrogen treatment in stroma, despite the coexpression of ERalpha and SRC-1 [3].
  • In the presence of RA, the coactivators SRC-1 and GRIP-1 formed complexes with RAR beta and RXR alpha which are bound to an oligonucleotide specifying a RARE site in the promoter [12].
  • Steroid co-activator 1 (SRC-1) enhances both constitutive and xenobiotic-induced CAR-mediated transactivation via the CYP2B1 PBRE in transfected primary hepatocytes [13].
  • The latter group, however, had significantly greater estrogen receptor alpha (ERalpha) expression in the olfactory bulb as compared to their younger counterparts, but very low expression of the steroid receptor coactivator, SRC-1 [14].

Analytical, diagnostic and therapeutic context of Ncoa1_predicted

  • Using RT-PCR, we have shown that expression of RARalpha, RXRalpha,TRalpha, ERalpha,ERbeta,N-CoR, SRC-1, SMRT and EGFR in rat was significantly increased in postlactating mammary gland when compared to that of nonlactating mammary tissue [15].
  • By using Northern and Western blot analysis we have estimated the mRNA and protein levels, respectively, of SRC-1 in the brain and pituitary of male and female rats, under physiological conditions and following restraint stress [16].


  1. Thyroid hormone exerts site-specific effects on SRC-1 and NCoR expression selectively in the neonatal rat brain. Iannacone, E.A., Yan, A.W., Gauger, K.J., Dowling, A.L., Zoeller, R.T. Mol. Cell. Endocrinol. (2002) [Pubmed]
  2. Steroid receptor coactivator-1 (SRC-1) mediates the development of sex-specific brain morphology and behavior. Auger, A.P., Tetel, M.J., McCarthy, M.M. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  3. Segregation of steroid receptor coactivator-1 from steroid receptors in mammary epithelium. Shim, W.S., DiRenzo, J., DeCaprio, J.A., Santen, R.J., Brown, M., Jeng, M.H. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  4. Thyroid hormone response elements differentially modulate the interactions of thyroid hormone receptors with two receptor binding domains in the steroid receptor coactivator-1. Takeshita, A., Yen, P.M., Ikeda, M., Cardona, G.R., Liu, Y., Koibuchi, N., Norwitz, E.R., Chin, W.W. J. Biol. Chem. (1998) [Pubmed]
  5. Truncated estrogen receptor product-1 suppresses estrogen receptor transactivation by dimerization with estrogen receptors alpha and beta. Resnick, E.M., Schreihofer, D.A., Periasamy, A., Shupnik, M.A. J. Biol. Chem. (2000) [Pubmed]
  6. Transcriptional regulation by a naturally occurring truncated rat estrogen receptor (ER), truncated ER product-1 (TERP-1). Schreihofer, D.A., Resnick, E.M., Soh, A.Y., Shupnik, M.A. Mol. Endocrinol. (1999) [Pubmed]
  7. Nuclear receptor coactivators modulate hormone-dependent gene expression in brain and female reproductive behavior in rats. Molenda, H.A., Griffin, A.L., Auger, A.P., McCarthy, M.M., Tetel, M.J. Endocrinology (2002) [Pubmed]
  8. Differential expression of p160 steroid receptor coactivators in the rat testis and epididymis. Igarashi-Migitaka, J., Takeshita, A., Koibuchi, N., Yamada, S., Ohtani-Kaneko, R., Hirata, K. Eur. J. Endocrinol. (2005) [Pubmed]
  9. SRC-1 localisation in lumbosacral spinal cord of male and female Wistar rats. Ranson, R.N., Santer, R.M., Watson, A.H. Neuroreport (2003) [Pubmed]
  10. RARbeta isoform-specific regulation of DARPP-32 gene expression: an ectopic expression study in the developing rat telencephalon. Liao, W.L., Liu, F.C. Eur. J. Neurosci. (2005) [Pubmed]
  11. Impact of maternal dietary exposure to endocrine-acting chemicals on progesterone receptor expression in microdissected hypothalamic medial preoptic areas of rat offspring. Takagi, H., Shibutani, M., Lee, K.Y., Masutomi, N., Fujita, H., Inoue, K., Mitsumori, K., Hirose, M. Toxicol. Appl. Pharmacol. (2005) [Pubmed]
  12. Regulation of alpha 2(I) collagen expression in stellate cells by retinoic acid and retinoid X receptors through interactions with their cofactors. Wang, L., Tankersley, L.R., Tang, M., Potter, J.J., Mezey, E. Arch. Biochem. Biophys. (2004) [Pubmed]
  13. Xenobiotic induction of cytochrome P450 2B1 (CYP2B1) is mediated by the orphan nuclear receptor constitutive androstane receptor (CAR) and requires steroid co-activator 1 (SRC-1) and the transcription factor Sp1. Muangmoonchai, R., Smirlis, D., Wong, S.C., Edwards, M., Phillips, I.R., Shephard, E.A. Biochem. J. (2001) [Pubmed]
  14. Neurotrophin expression in the reproductively senescent forebrain is refractory to estrogen stimulation. Jezierski, M.K., Sohrabji, F. Neurobiol. Aging (2001) [Pubmed]
  15. Expression of nuclear hormone receptors, their coregulators and type I iodothyronine 5'-deiodinase gene in mammary tissue of nonlactating and postlactating rats. Macejova, D., Baranova, M., Liska, J., Brtko, J. Life Sci. (2005) [Pubmed]
  16. Effects of gender and stress on the regulation of steroid receptor coactivator-1 expression in the rat brain and pituitary. Bousios, S., Karandrea, D., Kittas, C., Kitraki, E. J. Steroid Biochem. Mol. Biol. (2001) [Pubmed]
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