title: Hormonal regulation and functional role of vascular endothelial growth factor a in the rat testis.
abstract: Vascular endothelial cell growth factor (VEGF-A) is synthesized in the testis but its role and regulation in this organ have not been examined. VEGF and its receptors (VEGF-R) were quantified using reverse transcription-polymerase chain reaction and Western blot. VEGF, VEGF-R1, and VEGF-R2 mRNAs and VEGF protein were increased after treatment with 50 IU hCG. Injection of 100 ng human recombinant VEGF 165 into the testis caused an increase in endothelial cell proliferation, but only a moderate increase in testicular interstitial fluid volume. In contrast with systemic hCG treatment, local VEGF injection did not increase the permeability to intravenously injected colloidal carbon particles. However, if VEGF was given locally in the testes of animals pretreated with hCG 4 or 8 h earlier, VEGF acted in synergy with hCG to increase vascular carbon leakage by forming interendothelial cell gaps. Testicular blood flow was unaffected by local VEGF 165 injection. Treatment with a specific VEGF-R2 tyrosine kinase inhibitor blocked the hCG-induced increase in endothelial cell proliferation but did not affect the hCG-induced accumulation of polymorphonuclear leukocytes in testicular blood vessels or the increase in the testicular interstitial space. The present study demonstrated that testicular VEGF secretion is increased by hormonal stimulation of Leydig cells and that VEGF, through effects mediated via VEGF-R2, regulates endothelial cell proliferation in the rat testis. VEGF does not appear to regulate testicular blood flow and it is not involved in inducing the hCG-induced inflammation-like response in the testicular microvasculature. The permeability-increasing effect of VEGF is low in the testis under basal conditions but is apparently up-regulated by hCG treatment.
authors.affiliation: Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, S-901 85, Sweden.
authors.forename: Stina Häggström
authors.initials: SH
authors.lastname: Rudolfsson
authors.forename: Pernilla
authors.initials: P
authors.lastname: Wikström
authors.forename: Andreas
authors.initials: A
authors.lastname: Jonsson
authors.forename: Ola
authors.initials: O
authors.lastname: Collin
authors.forename: Anders
authors.initials: A
authors.lastname: Bergh
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013737:Testis / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D006063:Chorionic Gonadotropin; D010880:Piperidines; D011799:Quinazolines; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; C452423:vandetanib