Steroid receptor coactivator 3 maintains circulating insulin-like growth factor I (IGF-I) by controlling IGF-binding protein 3 expression.

Molecular and Cellular Biology
Lan LiaoJianming Xu

Abstract

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 limit...Continue Reading

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Citations

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