Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2028631 | Steroids | 2009 | 8 Pages |
Abstract
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 24Â h in a dose-dependent manner (10â5, 10â6 and 10â7Â M) and in a time-dependent fashion (1, 3, 6, 12 and 24Â h) at a high concentration (10â5Â 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 24Â h. ED-exposure induced a marked increase in GH gene transcription as early as 6Â h and peaked at 12Â 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 24Â 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 24Â 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.
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Vu Hoang Dang, Thi Hoa Nguyen, Geun-Shik Lee, Kyung-Chul Choi, Eui-Bae Jeung,