Functional analysis of LH/hCG receptor in human placental chorionic villous macrophages

• Project/Area Number: 15591763
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Kumamoto University
• Principal Investigator: KATABUCHI Hidetaka Kumamoto University, Faculty of Medical and Pharmaceutical Sciences, Professor, 大学院・医学薬学研究部, 教授 (90224451)
• Co-Investigator(Kenkyū-buntansha): OHBA Takashi Kumamoto University, Faculty of Medical and Pharmaceutical Sciences, Professor, 大学院・医学薬学研究部, 助教授 (50244132) ; TASHIRO Hironori Kumamoto University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (70304996)
• Project Period (FY): 2003 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000); Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000); Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: Placenta / Villi / Macrophage / LH-hCG receptor / exon 9-deleted LH-hCG receptor / THP-1 cell / hCG / hCG β subunit core fragment / hCGβ subunit core fragment / hCG β subunit core fragment / hCGβsubunit core fragment

Research Abstract

Human gonads and non-gonadal organs/tissues express LH/CG receptors. This study aimed to identify the LH/CG receptors and to clarify their function in human placental chorionic villous macrophages. Macrophages as well as syncytiotrophoblasts of human chorionic villous tissues were immunohistochemically positive for LH/CG receptor throughout gestation. By RT-PCR, villous macrophages were shown to express a variant type of LH/CG receptor, the sequencing of which revealed a deletion of exon 9. For experiments in vitro, a monocyte-macrophage cell line, THP-1, was transfected with vector alone, wild-type LH/CG receptor, and exon 9-deleted LH/CG receptor after phorbol 12-myristate 13-acetate (PMA) treatment. Non-PMA-treated THP-1 cells transfected with vector alone were also examined. THP-1 cells expressed exon 9-deleted LH/CG receptor after treatment with PMA. After the cells of the four groups were cultured in medium containing intact hCG, the concentrations of hCG and its b-core fragment (β-CF) were measured in the supernatant of the culture medium and in the cell cytosol. Time-dependent hCG uptake was observed in both non-PMA-treated and PMA-treated THP-1 cells, suggesting that the variant receptor is not directly involved in the ingestion of hCG. The degradation of hCG and excretion of β-CF were progressed in PMA-treated cells but not in the un-treated cells. In the cell cytosol, the ratio of β-CF and hCG concentrations (β-CF/hCG) was significantly higher in the PMA-treated cells than in non-PMA-treated cells ; however, it did not differ between the PMA-treated cells transfected with exon 9-deleted receptor and those transfected with vector alone. Macrophages may express the variant receptor in order to recognize the intracytoplasmic hCG and transport it to the lysosome. Among the two PMA-treated cells, the ratio was lower in those transfected with wild-type receptor. The expression of the variant receptor may modulate the degradation of hCG but be reduced by expression of the wild-type receptor in its lacking macrophages. Our data suggest a potentially important role for exon 9-deleted LH/CG receptors expressed in human placental villous macrophages in the local metabolism of hCG.

Research Products

• [Journal Article] Characterization of 17beta-hydroxysteroid dehydrogenase type 4 in human ovarian surface epithelial cell. (2006)
  • Author(s): Nagayoshi Y, Ohba T, Yamamoto H, Miyahara Y, Tashiro H, Katabuchi H, et al.
  • Journal Title: Mol Hum Reprod 11 Pages: 615-621
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Characterization of 17beta-hydroxysteroid dehydrogenase type 4 in human ovarian surface epithelial cells. (2006)
  • Author(s): Nagayoshi Y, Ohba T, Yamamoto H, Miyahara Y, Tashiro H, Katabuchi H, et al.
  • Journal Title: Mol Hum Reprod 11 Pages: 615-621
• [Journal Article] Neonatal estrogenic exposure suppresses PTEN-related endometrial carcinogenesis in recombinant mice. (2006)
  • Author(s): Begum M, Tashiro H, Katabuchi H, et al.
  • Journal Title: Lab Invest 86 Pages: 286-296
• [Journal Article] Expression of variant luteinizing hormone/chorionic gonadotropin receptors and degradation of chorionic gonadotropin in human chorionic villous macrophages. (2005)
  • Author(s): Sonoda N, Katabuchi H, Tashiro H et al.
  • Journal Title: Placenta 26 Pages: 298-307
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Pathophysiological dynamics of human ovarian surface epithelial cells in epithelial ovarian carcinogenesis. (2005)
  • Author(s): Okamura H, Katabuchi H.
  • Journal Title: Int Rev Cytol 242 Pages: 1-54
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Establishment of an immortalised human ovarian surface epithelial cell line without chromosomal instability. (2005)
  • Author(s): Maeda T, Tashiro H, Katabuchi H, et al.
  • Journal Title: Br J Cancer 93 Pages: 116-123
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Histologic type,organ of origin,and Wnt pathway status : effect on gene expression in ovarian and uterine carcinomas. (2005)
  • Author(s): Shedden KA, Kshirsagar MP, Schwartz DR, Wu R, Yu H, Misek DE, Hanash S, Katabuchi H, et al.
  • Journal Title: Clin Cancer Res 11 Pages: 2123-2131
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression of variant luteinizing hormone/chorionic gonadotropin receptors and degradation of chorionic gonadotropin in human chorionic villous macrophages. (2005)
  • Author(s): Sonoda N, Katabuchi H, Tashiro H, et al.
  • Journal Title: Placenta 26 Pages: 298-307
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Histologic type, organ of origin, and Wnt pathway status : effect on gene expression in ovarian and uterine carcinomas. (2005)
  • Author(s): Shedden KA, Kshirsagar MP, Schwartz DR, Wu R, Yu H, Misek DE, Hanash S, Katabuchi H, et al.
  • Journal Title: Clin Cancer Res 11 Pages: 2123-2131
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Histologic type, organ of origin, and Wnt pathway status: effect on gene expression in ovarian and uterine carcinomas (2005)
  • Author(s): Shedden KA, Kshirsagar MP, Schwartz DR, Wu R, Yu H, Misek DE, Hanash S, Katabuchi H, et al.
  • Journal Title: Clin Cancer Res 11 Pages: 2123-2131
• [Journal Article] Pathophysiological dynamics of human ovarian surface epithelial cells in epithelial ovarian carcinogenesis, review (2005)
  • Author(s): Okamura H., Katabuchi H.
  • Journal Title: International review of cytology 242 Pages: 1-54
• [Journal Article] Expression of variant luteinizing hormone/chorionic gonadotropin receptors and degradation of chorionic gonadotropin in human chorionic villous macrophages (2005)
  • Author(s): Sonoda N., Katabuchi H., et al.
  • Journal Title: Placenta (In press)
• [Publications] N.Sageshima, et al.: "Necrotic feature of the trophoblasts lacking HLA-G expression in normal and preeclamptic placentas"American Journal of Reproductive Immunology. 49. 174-182 (2003)
• [Publications] H.Katabuchi, et al.: "Characterization of macrophages in the decidual atherotic spiral artery with special reference to the cytology of foam cells"Medical Electron Microscopy. 36. 253-262 (2003)