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Biology of reproduction2001; 65(1); 197-203; doi: 10.1095/biolreprod65.1.197

Epidermal growth factor regulation of equine glycoprotein hormone alpha subunit expression in trophoblast cells.

Abstract: Primates and equids are the only species known to express the placental glycoprotein hormone, chorionic gonadotropin (CG), a heterodimeric glycoprotein composed of an alpha subunit linked to a hormone-specific beta subunit. The regulatory mechanisms involved in the induction of equine glycoprotein alpha 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 alpha subunit gene by EGF in trophoblasts. We found that 2800 base pairs of 5' flanking sequence from the equine alpha 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 alpha 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 alpha 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 alpha 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.
Publication Date: 2001-06-23 PubMed ID: 11420240DOI: 10.1095/biolreprod65.1.197Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

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The research article examines how Epidermal Growth Factor (EGF) controls the expression of the equine glycoprotein hormone alpha subunit gene in trophoblast cells, which are crucial components of placental structure in animals.

Article Explanation

  • The study is based on the fact that primates and equids (a group that includes horses) are the only species known to express the placental glycoprotein hormone, chorionic gonadotropin (CG). This is a compound protein made of an alpha subunit tied to a hormone-specific beta subunit.
  • The mechanisms behind the regulation of the equine glycoprotein alpha subunit gene expression have not been previously identified, and this research aims at filling this knowledge gap.
  • The Epidermal Growth Factor (EGF) receptor is known to transmit signals that modify various cell functions, including cell proliferation, differentiation, hormone secretion, and gene regulation. Note that EGF is a protein that stimulates cell growth.
  • The investigation in this research revolves around how EGF regulates the equine alpha subunit gene in trophoblasts. Trophoblasts are cells providing nutrients to the embryo and developing into a large part of the placenta.
  • The findings show that the equine alpha subunit gene could be activated by EGF and phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator. PKC is an enzyme associated with several signal transduction processes.
  • When the EGF receptor blocks the inhibitor of PKC, called bisindolylmaleimide-I, it was suggested that PKC is involved in the pathway downstream of EGF.
  • Moreover, when PD98059, an inhibitor of the extracellular signal-regulated kinase (ERK) pathway, completely blocked the equine alpha promoter’s activation by PMA, it suggested that the mitogen-activated protein kinase (MAPK) cascade is involved downstream of the PKC pathway.
  • Therefore, it’s concluded that the EGF/PKC/MAPK pathway regulates equine glycoprotein alpha subunit gene expression through a distinctive regulatory region in trophoblasts, and essential elements for the baseline expression exist within a specific region of the promoter.

Cite This Article

APA
Thway TM, Wolfe MW. (2001). Epidermal growth factor regulation of equine glycoprotein hormone alpha subunit expression in trophoblast cells. Biol Reprod, 65(1), 197-203. https://doi.org/10.1095/biolreprod65.1.197

Publication

ISSN: 0006-3363
NlmUniqueID: 0207224
Country: United States
Language: English
Volume: 65
Issue: 1
Pages: 197-203

Researcher Affiliations

Thway, T M
  • Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160-7401, USA.
Wolfe, M W

    MeSH Terms

    • Animals
    • Cells, Cultured
    • Enzyme Activators / pharmacology
    • Enzyme Inhibitors / pharmacology
    • Epidermal Growth Factor / physiology
    • Female
    • Flavonoids / pharmacology
    • Glycoprotein Hormones, alpha Subunit / biosynthesis
    • Horses / physiology
    • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
    • Plasmids / genetics
    • Promoter Regions, Genetic / drug effects
    • Protein Kinase C / metabolism
    • Signal Transduction / drug effects
    • Tetradecanoylphorbol Acetate / pharmacology
    • Transfection
    • Trophoblasts / cytology
    • Trophoblasts / metabolism

    Grant Funding

    • HD 33994 / NICHD NIH HHS
    • R29 DK50668 / NIDDK NIH HHS

    Citations

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