Epidermal Growth Factor Regulation of Equine Glycoprotein Hormone α Subunit Expression in Trophoblast Cells1

• Published in: Biology of reproduction 2001-07, Vol.65 (1), p.197-203
• Main Authors: Thway, Theingi M, Wolfe, Michael W
• Format: Article
• Language: English
• Subjects: Contents; gene regulation; placenta; signal transduction; trophoblast
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod65.1.197

Primates and equids are the only species known to express the placental glycoprotein hormone, chorionic gonadotropin (CG), a heterodimeric glycoprotein composed of an α subunit linked to a hormone-specific β subunit. The regulatory mechanisms involved in the induction of equine glycoprotein α subunit gene expression have not been identified. Epidermal growth factor (EGF) receptor is known to transduce signals that alter a number of different cellular functions (cell proliferation, differentiation, hormone secretion, and gene regulation). In the present study, we investigated the regulation of the equine α subunit gene by EGF in trophoblasts. We found that 2800 base pairs of 5′ flanking sequence from the equine α subunit promoter is sufficient for basal expression in human choriocarcinoma cells. Epidermal growth factor and phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), increased transcriptional activity of the equine α subunit promoter (−2800/+21). These responses were blocked by pretreatment with bisindolylmaleimide-I, an inhibitor of PKC, suggesting an involvement of this pathway downstream of EGF. In addition, PD98059, an inhibitor of the extracellular signal-regulated kinase (ERK) pathway, completely blocked activation of the equine α promoter by PMA, suggesting that mitogen-activated protein kinase (MAPK) cascade was involved downstream of the PKC pathway. In conclusion, the EGF/PKC/MAPK pathway regulates equine glycoprotein α subunit gene expression through a distinct regulatory region (−2300 to −1900) in trophoblasts, while essential elements for basal expression appear to exist within the −2800 to −1900 region of the promoter.