Assessing placental corticotrophin-releasing hormone disruption by hexestrol in a cell model.
Studies have shown that corticotrophin-releasing hormone (CRH) and relaxin are associated with early delivery. Our lab previously has shown the mycotoxin zeranol increases placental CRH expression. The mycotoxin is used in the farming industry to promote cattle growth, and some synthetic hormones are also used for the same purposes. In order to complete the picture of these growth promoting agents, we attempted to examine the synthetic hormones on the placental gene expression in the current study. Among the tested compounds, hexestrol induced the CRH mRNA and protein expression at 100nM in JEG-3 cells. As signal transduction pathways have been described in the transcriptional control previously, the activations of several protein kinases were determined. P38, PKCβ and JNK were activated upon hexestrol treatment. Since the P38-inhibitor SB203580 prevented hexestrol from inducing CRH in a subsequent experiment, P38 was likely involved in the transcriptional regulation. Electrophoretic mobility shift assay revealed an increase in the CRE binding activity in CRH promoter. This study showed that hexestrol exposure might be a concern for pregnant women.
Food and Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
Yun
Y
Zhu
Food and Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
Yan
Y
Qin Tan
Food and Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong; Biochemistry Programme, School of Life Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong. Electronic address: laikleung@cuhk.edu.hk.
Lai K
LK
Leung
D001665:Binding Sites; D018929:Cell Culture Techniques; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006589:Hexestrol / Q000633:toxicity*; D006801:Humans; D010920:Placenta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
D004268:DNA-Binding Proteins; D004968:Estrogens, Non-Steroidal; D012333:RNA, Messenger; D006589:Hexestrol; D003346:Corticotropin-Releasing Hormone
CRH; Hexestrol; Placental cells