Expression of vascular endothelial growth factor A during ligand-induced down-regulation of luteinizing hormone receptor in the ovary.
Vascular endothelial growth factor A (VEGF-A) is one of the most important regulators of ovarian angiogenesis. In this study, we examined the temporal relationship between VEGF-A and luteinizing hormone receptor (LHR) mRNA expression during ligand-induced down-regulation of LHR. Immature female rats were treated with pregnant mare's serum gonadotropin followed by 25 IU hCG 56 h later (day 0). On day 5, treatment with hCG (50 IU) to down-regulate LHR showed a temporal decrease in VEGF-A mRNA and protein levels in parallel with decreasing LHR mRNA. This effect was specific since the expression of CYP11A1 mRNA showed no decline. Examination of VEGF-A mRNA expression, using in situ hybridization histochemistry with (35)S-labeled antisense VEGF-A mRNA probe, showed intense signal in the corpora lutea on day 5. Treatment with 50 IU hCG to down-regulate LHR mRNA showed a decline in the intensity of VEGF-A mRNA in the corpora lutea. VEGF-A mRNA expression returned to control level 53 h later when the expression of LHR mRNA also recovered. These results show that the transient down-regulation of VEGF-A mRNA and protein closely parallels the ligand-induced down-regulation of LHR mRNA. The present study establishes a close association between VEGF-A and LHR mRNA expression, suggesting the possibility that VEGF-A-induced vascularization of the ovary is dictated by the expression of LHR and this might play a regulatory role in ovarian physiology.
Harada
M
M
Department of Obstetrics/Gynecology, University of Michigan Medical School, Ann Arbor, MI 48109-0278, United States.
Peegel
H
H
Menon
K M J
KM
D000818:Animals; D002469:Cell Separation; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008024:Ligands; D008184:Luteal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007986:Luteinizing Hormone / Q000494:pharmacology*; D010053:Ovary / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011974:Receptors, LH / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D006063:Chorionic Gonadotropin; D008024:Ligands; D012333:RNA, Messenger; D011974:Receptors, LH; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D007986:Luteinizing Hormone