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Vascular endothelial growth factor production by human luteinized granulosa cells in vitro.
- Source :
-
Human reproduction (Oxford, England) [Hum Reprod] 1997 Dec; Vol. 12 (12), pp. 2756-61. - Publication Year :
- 1997
-
Abstract
- Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) originating from the follicle or corpus luteum may be a physiological regulator of ovulation and neovascularization of luteinizing tissue, as well as a pathological factor in the development of ovarian hyperstimulation syndrome (OHSS). The objective of this study was to quantify VEGF production by human luteinized granulosa cells in vitro and to determine if gonadotrophin stimulates VEGF production directly and/or indirectly via enhanced synthesis of progesterone. In study 1, luteinized granulosa cells collected from women undergoing ovarian stimulation for in-vitro fertilization were cultured in the presence and absence of human chorionic gonadotrophin (HCG; 100 ng/ml) and/or low density lipoprotein (LDL; 100 microg protein/ml). In study 2, the progesterone synthesis inhibitor trilostane (250 ng/ml) and/or a progesterone receptor antagonist ZK137.316 (3.2 microM) were also added. Medium was harvested on days 1, 3, 5, 7 and 9 of culture and assayed for VEGF and progesterone. Results of study 1 were divided into two categories based on control concentrations of VEGF on day 1: 'low producers' (n = 6; <750 pg VEGF/ml) and 'high producers' (n = 5; >1000 pg VEGF/ml; P < 0.01). VEGF concentrations in cultures of both low and high producers increased (P < 0.01) from day 1 to maximal values on day 3, then steadily declined through to day 9. Chronic exposure to LDL or HCG increased (P < 0.05) VEGF concentrations in cultures of low producers by day 3 and day 5 respectively. In contrast, LDL did not alter VEGF concentrations in cultures of high producers and HCG did not increase VEGF concentrations until day 7. Nevertheless, acute exposure to HCG beginning on day 7 increased (P < 0.05) VEGF concentrations 3-fold in cultures of low or high producers. In study 2, trilostane treatment decreased (P < 0.05) progesterone concentrations by 91% on day 1 of culture but had no effect on VEGF concentrations on any day. ZK137.316 alone or with trilostane did not affect VEGF synthesis. These results suggest that VEGF production by luteinized granulosa cells is enhanced by gonadotrophin (HCG) independent of gonadotrophin-stimulated progesterone synthesis. These data are consistent with the hypothesis that the exacerbation of OHSS in early pregnancy is mediated by the CG stimulation of luteal VEGF production.
- Subjects :
- Adult
Cells, Cultured
Chorionic Gonadotropin pharmacology
Dihydrotestosterone analogs & derivatives
Dihydrotestosterone pharmacology
Female
Humans
Lipoproteins, LDL pharmacology
Progesterone antagonists & inhibitors
Progesterone biosynthesis
Receptors, Progesterone antagonists & inhibitors
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Corpus Luteum physiology
Endothelial Growth Factors biosynthesis
Granulosa Cells metabolism
Lymphokines biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0268-1161
- Volume :
- 12
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Human reproduction (Oxford, England)
- Publication Type :
- Academic Journal
- Accession number :
- 9455848
- Full Text :
- https://doi.org/10.1093/humrep/12.12.2756