| First Author | Liao L | Year | 2008 |
| Journal | Mol Cell Biol | Volume | 28 |
| Issue | 7 | Pages | 2460-9 |
| PubMed ID | 18212051 | Mgi Jnum | J:134212 |
| Mgi Id | MGI:3785136 | Doi | 10.1128/MCB.01163-07 |
| Citation | Liao L, et al. (2008) Steroid receptor coactivator 3 maintains circulating insulin-like growth factor I (IGF-I) by controlling IGF-binding protein 3 expression. Mol Cell Biol 28(7):2460-9 |
| abstractText | Steroid receptor coactivator 3 (SRC-3/AIB1/ACTR/NCoA-3) is a transcriptional coactivator for nuclear receptors including vitamin D receptor (VDR). Growth hormone (GH) regulates insulin-like growth factor I (IGF-I) expression, and IGF-I forms complexes with acid-labile subunit (ALS) and IGF-binding protein 3 (IGFBP-3) to maintain its circulating concentration and endocrine function. This study demonstrated that the circulating IGF-I was significantly reduced in SRC-3(-/-) mice with the C57BL/6J background. However, SRC-3 deficiency affected neither GH nor ALS expression. The low IGF-I level in SRC-3(-/-) mice was not due to the failure of IGF-I mRNA and protein synthesis but was a consequence of rapid degradation. The rapid IGF-I degradation was associated with drastically reduced IGFBP-3 levels. Because IGF-I and IGFBP-3 stabilize each other, SRC-3(-/-) mice were crossbred with the liver-specific transthyretin (TTR)-IGF-I transgenic mice to assess the relationship between reduced IGF-I and IGFBP-3. In SRC-3(-/-)/TTR-IGF-I mice, the IGF-I level was significantly increased over that in SRC-3(-/-) mice, but the IGFBP-3 level failed to increase proportionally, indicating that the low IGFBP-3 level is a responsible factor that limits the IGF-I level in SRC-3(-/-) mice. Furthermore, IGFBP-3 mRNA was reduced in SRC-3(-/-) mice. The IGFBP-3 promoter activity induced by vitamin D, through VDR, was diminished in SRC-3(-/-) cells, suggesting an important role of SRC-3 in VDR-mediated transactivation of the IGFBP-3 gene. In agreement with the role of SRC-3 in VDR function, the expression of several VDR target genes was also reduced in SRC-3(-/-) mice. Therefore, SRC-3 maintains IGF-I in the circulation through enhancing VDR-regulated IGFBP-3 expression. |
