Hormonal Regulation and Functional Role of Vascular Endothelial

21 Vascular endothelial cell growth factor (VEGF-A) is synthesized in the testis but its role and 22 regulation in this organ have not been examined. VEGF and its receptors were quantified using 23 RT-PCR and Western blot. VEGF, VEGF-R1, and VEGF-R2 mRNAs and VEGF protein were 24 increased after treatment with 50 i.u. hCG. Injection of 100 ng human recombinant VEGF 165 25 into the testis caused an increase in endothelial cell proliferation, but only a moderate increase in 26 testicular interstitial fluid volume. In contrast to systemic hCG treatment, local VEGF injection 27 did not increase the permeability to intravenously injected colloidal carbon particles. However, if 28 VEGF was given locally in the testes of animals pretreated with hCG 4 or 8 h earlier VEGF acted 29 in synergy with hCG to increase vascular carbon leakage by forming inter endothelial cell gaps. 30 Testicular blood flow was unaffected by local VEGF 165 injection. Treatment with a specific 31 VEGF-R2 tyrosine kinase inhibitor blocked the hCG-induced increase in endothelial cell 32 proliferation, but did not affect the hCG-induced accumulation of polymorphnuclear leukocytes 33 in testicular blood vessels or the increase in the testicular interstitial space. The present study 34 demonstrated that testicular VEGF secretion is increased by hormonal stimulation of Leydig cells 35 and that VEGF, through effects mediated via VEGF-R2, regulates endothelial cell proliferation in 36 the rat testis. VEGF does not appear to regulate testicular blood flow and it is not involved in 37 inducing the hCG-induced inflammation-like response in the testicular microvasculature. The 38 permeability increasing effect of VEGF is low in the testis under basal conditions but apparently 39 up-regulated by hCG treatment. 40