In vitro
- 作者：Vu Hoang Dang ; Thi Hoa Nguyen ; Geun-Shik Lee ; Kyung-Chul Choi ; Eui-Bae Jeung
- 关键词：Growth hormone ; GH3 cell line ; Endocrine disruptors ; Estrogenicity
- 刊名：Steroids
- 出版年：2009
- 期刊代码：142_0039128x
- 类别：bio
- 出版时间：11 August 2009
- 卷：74
- 期：8
- 页码：707-714
- 文件大小：1044 K
摘要
In this study, we employed an in vitro model to examine the effects of endocrine disruptors (EDs) in the regulation of growth hormone (GH) gene, an important hormone in growth, development and body composition. The rat pituitary cells, GH3, were treated with alkyl-phenols (APs), i.e., 4-tert-octyl-phenol (OP), p-nonyl-phenol (NP) or bisphenol A (BPA) for 24 h in a dose-dependent manner (10−5, 10−6 and 10−7 M) and in a time-dependent fashion (1, 3, 6, 12 and 24 h) at a high concentration (10−5 M). An anti-estrogen, ICI 182,780, was used to examine the potential involvement of estrogen receptor (ER) in the induction of GH by EDs through an ER-mediated pathway. Treatment with OP, NP and BPA induced a significant increase in GH gene expression at high and medium doses at 24 h. ED-exposure induced a marked increase in GH gene transcription as early as 6 h and peaked at 12 h. Co-treatment with ICI 182,780 significantly attenuated ED-induced GH expression in GH3 cells. Interestingly, the level of in vitro GH release was significantly increased at 24 h in response to OP, NP or BPA, whereas co-treatment with ICI 182,780 significantly reversed ED-induced GH secretion, indicating that ER may take part in both GH gene transcription and its release in these cells. In addition, the activation of extracellular signal-regulated kinases (ERKs), protein kinases B (Akt) or G protein in response to OP, NP or BPA at 24 h was observed in this study. Exposure to these APs resulted in a rapid and significant activation of ERK phosphorylation, reflecting that EDs-induced response may involve both genomic and non-genomic pathways in these cells. Taken together, these results may provide new insight into the mode of ED-induced action in GH gene regulation as well as the biological pathway underlying these molecular events.