Luteogenic hormones act through a vascular endothelial growth factor-dependent mechanism to up-regulate alpha 5 beta 1 and alpha v beta 3 integrins, promoting the migration and survival of human luteinized granulosa cells.
The formation of the corpus luteum (CL) is critical for the establishment of a successful pregnancy. After ovulation, the CL develops from the remnants of the ovulated ovarian follicle. This process, which involves varying cell-matrix interactions, is poorly characterized. To understand the role and potential regulation of cell-matrix interactions in the formation of the CL, we investigated the expression and activity of the matrix protein fibronectin (FN) and several of its integrin receptors on luteinized granulosa cells (GCs). In situ, FN and several FN-binding integrins were detected around luteinizing GCs during the early luteal phase, although expression declined in the late luteal phase. In vitro, GCs released FN, and stimulation of these cells with human chorionic gonadotropin increased the surface expression of FN, alpha(5)beta(1), and alpha(v)beta(3). Up-regulation of these proteins on GCs was reproduced by stimulation with vascular endothelial growth factor (VEGF) and was inhibited by anti-VEGF antibody. Lastly, expression of alpha(5)beta(1) and alpha(v)beta(3) mediated adhesion to FN, facilitated migration, and prevented apoptosis. These data suggest that in vivo luteogenic hormones, in part through a VEGF-dependent mechanism, stimulate selected integrin-matrix adhesive interactions that promote the motility and survival of GCs and thus contribute to the formation and preservation of the CL.
Rolaki
Alexandra
A
Laboratory of Human Reproduction, Department of Obstetrics and Gynaecology, Medical School, University of Crete, Heraklion 71110, Greece.
Coukos
George
G
Loutradis
Dimitris
D
DeLisser
Horace M
HM
Coutifaris
Christos
C
Makrigiannakis
Antonis
A
D000328:Adult; D017209:Apoptosis; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism; D005260:Female; D005300:Fertility Agents, Female / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006065:Gonadotropins, Pituitary / Q000378:metabolism*; D006107:Granulosa Cells / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D039482:Integrin alpha5 / Q000378:metabolism*; D016729:Leuprolide / Q000494:pharmacology; D008597:Menstrual Cycle / Q000502:physiology; D011247:Pregnancy; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D006063:Chorionic Gonadotropin; D005300:Fertility Agents, Female; D005353:Fibronectins; D006065:Gonadotropins, Pituitary; D039482:Integrin alpha5; D042461:Vascular Endothelial Growth Factor A; D005640:Follicle Stimulating Hormone; D016729:Leuprolide