The Alcohol‐Induced Suppression of Ovarian Insulin‐Like Growth Factor‐1 Gene Transcription Is Independent of Growth Hormone and Its Receptor
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BACKGROUND: Insulin-like growth factor-1 (IGF-1) plays an important role in ovarian development and function. Alcohol (ALC) is a gonadal toxin and capable of causing depressed ovarian IGF-1 and suppressed estradiol. The mechanism by which ALC affects IGF-1 transcription is not well understood, and more information is needed to better understand the interrelationships between ALC, growth hormone (GH) and its ovarian receptor, and the gene expression of ovarian IGF-1. METHODS: Prepubertal transgenic mice carrying the bovine GH (bGH) gene were fed either a liquid diet containing ALC, pair-fed the companion isocaloric control liquid diet, or fed chow and water. A fourth group consisted of normal (nontransgenic) littermates fed chow and water. Mice received their diets for 5 days, were then killed and tissues collected and frozen. RESULTS: Alcohol did not alter circulating levels of bGH held constant by the promoter. Real-time polymerase chain reaction (PCR) showed elevated (p<0.05) ovarian IGF-1 mRNA levels in both groups of transgenic control mice, compared with normal mice. Insulin-like growth factor-1 expression in the ALC-treated transgenic mice was suppressed (p<0.01) compared with both transgenic controls. Insulin-like growth factor-1 receptor (IGF-1R) gene expression was also decreased (p<0.01) in ALC-treated transgenic mice compared with transgenic controls. Growth hormone-receptor (GH-R) synthesis revealed that all transgenic mice, including those exposed to ALC, showed increased (p<0.05) GH-R mRNA compared with normal controls, and ALC did not alter protein levels of the GH-R. CONCLUSIONS: These results suggest that the ALC-induced suppression of ovarian IGF-1 gene transcription is independent of alterations in serum GH.
author list (cited authors)
Srivastava, V. K., Hiney, J. K., Mattison, J. A., Bartke, A., & Dees, W. L.
complete list of authors
Srivastava, Vinod K||Hiney, Jill K||Mattison, Julie A||Bartke, Andrej||Dees, W Les