ヒト黄体細胞分化抗原の同定とその黄体機能調節における意義(シンポジウム1 黄体機能の調節とその異常)

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To clarify the new molecules that are involved in the regulation for ovarian cell differentiation and function, we raised murine monoclonal antibodies (mAbs) against human ganulosa cells and luteal cells. By analyzing the antigenic proteins, we confirmed that various molecules are expressed on human luteal cells and showed that they are deeply concerned with ovarian cell differentiation and function. The defined molecules are largely classified into three groups ; 1, integrin-related cell adhesion molecules ; 2, membrane-bound peptidases ; 3, T-lymphocyte-related molecules. Integrin α6β1 was revealed to be expressed on human luteal cells by analyzing the molecule detected by OG-1 mAb. Laminin, which is a ligand of integrin α6β1, was shown to suppress progesterone production by luteinizing granulosa cells. The anti-integrin α6β1 mAb GoH3, which specifically blocks the interaction between integrin α6β1 and laminin, promoted progesterone production by luteinizing granulosa cells. Integrin α5β1 and its ligand, fibronectin, are also expressed on luteinization of granulosa cells. The intrabursal administration of the specific blocking mAb against integrin α5β1 into pseudopregnant mice enhanced progesterone production by early corpora lutea. These findings suggest that the interaction of integrins and extracellular matrix regulates luteinization of granulosa cells. Membrane-bound peptidases exist on the cell surface and can metabolize biological active peptides extracellularly before they bind to their specific receptors. Human luteal cells express several membrane-bound peptidases such as aminopeptidase N, diptidyl peptidase IV (DPPIV), and carboxypeptidase M. The inhibitor of aminopeptidase, bestatin, augmented the progesterone production by porcine cultured granulosa cells, in which luteinization was induced by LH treatment. In addition, intrabursal administration of bestatin into pseudopregnant mice increased serum progesterone level, indicating that membrane-bound aminopeptidases are involved in luteal cell function. DPPIV progressingly appears on luteinizing granulosa cells 4 days after ovulation. Flow cytometric analysis showed that TNF-α and IL-1 stimulated the expression of DPPIV on cultured human luteinizing granulosa cells, whereas hCG had no effect on it. Leukocyte functional antigen (LFA)-3 is another molecule expressed on granulosa cells during the process of luteinization, which is a ligand for CD2 antigen expressed on pan-T-lymphocytes. Flow cytometrical analysis demonstrated that TNF-α, but not the hCG, significantly enhanced LFA-3 expression. The HCL-1 antigen detected by newly raised monoclonal antibody against human corpora lutea, becomes rapidly expressed on luteinizing granulosa cells during corpus luteum formation. Flow cytometry showed that hCG significantly suppressed the expression of HCL-1 antigen. These findings suggest that dual controls of endocrine and immune systems operate for adequate maturation of human granulosa cells in corpus luteum formation. Human leukocyte antigen (HLA)-DR and LFA-3 were also shown to be expressed on large luteal cells in corpus luteum pregnancy, suggesting physiological interaction between T lymphocytes and luteal cells during early pregnancy. The coculture of luteal cells and peripheral mononuclear cells derived from early pregnant women promoted progesterone production. These findings suggest that the interaction between luteal cells and immune cells are involved in the differentiation of menstrual corpus luteum into pregnancy corpus luteum and the maintenance of pregnancy corpus luteum.
社団法人日本産科婦人科学会の論文
1998-08-01

ヒト黄体細胞分化抗原の同定とその黄体機能調節における意義(シンポジウム1 黄体機能の調節とその異常)

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