hCG-dependent regulation of angiogenic factors in human granulosa lutein cells.
As prerequisite for development and maintenance of many diseases angiogenesis is of particular interest in medicine. Pathologic angiogenesis takes place in chronic arthritis, collagen diseases, arteriosclerosis, retinopathy associated with diabetes, and particularly in cancers. However, angiogenesis as a physiological process regularly occurs in the ovary. After ovulation the corpus luteum is formed by rapid vascularization of initially avascular granulosa lutein cell tissue. This process is regulated by gonadotropic hormones. In order to gain further insights in the regulatory mechanisms of angiogenesis in the ovary, we investigated these mechanisms in cell culture of human granulosa lutein cells. In particular, we determined the expression and production of several angiogenic factors including tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), Leptin, connective tissue growth factor (CTGF), meningioma-associated complimentary DNA (Mac25), basic fibroblast growth factor (bFGF), and Midkine. In addition, we showed that human chorionic gonadotropin (hCG) has distinct effects on their expression and production. hCG enhances the expression and production of TIMP-1, whereas it downregulates the expression of CTGF and Mac25. Furthermore it decreases the expression of Leptin. Our results provide evidence that hCG determines growth and development of the corpus luteum by mediating angiogenic pathways in human granulosa lutein cells. Hence we describe a further approach to understand the regulation of angiogenesis in the ovary.
Phan
B
B
Department of Obstetrics and Gynecology, Freiburg University Medical Center, Freiburg, Germany.
Rakenius
A
A
Pietrowski
D
D
Bettendorf
H
H
Keck
C
C
Herr
D
D
D043925:Angiogenesis Inducing Agents / Q000737:chemistry; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D055513:Connective Tissue Growth Factor; D016207:Cytokines / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics; D006107:Granulosa Cells / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D020738:Leptin / Q000235:genetics; D008184:Luteal Cells / Q000378:metabolism*; D000078792:Midkine; D018919:Neovascularization, Physiologic; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D015854:Up-Regulation
D043925:Angiogenesis Inducing Agents; C526317:CCN2 protein, human; D006063:Chorionic Gonadotropin; D016207:Cytokines; D017874:Immediate-Early Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D019715:Tissue Inhibitor of Metalloproteinase-1; C102529:insulin-like growth factor binding protein-related protein 1; D000078792:Midkine; D055513:Connective Tissue Growth Factor; D005346:Fibroblast Growth Factors