Endocrine gland-derived vascular endothelial growth factor in rat pancreas: genetic expression and testosterone regulation.
Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an endothelial cell mitogen, expressed essentially in steroidogenic cells. Recently, the expression of EG-VEGF in normal human pancreas and pancreatic adenocarcinoma has been demonstrated. Epidemiologically, pancreatic carcinogenesis is more frequent in males than females, and given that androgen receptors and testosterone biotransformation have been described in pancreas, we hypothesized that testosterone could participate in the regulation of EG-VEGF expression. In this study, we investigated the regulation of EG-VEGF gene expression by testosterone in normal rat pancreatic tissue and rat insulinoma cells (RINm5F). Total RNA was extracted from rat pancreas and cultured cells. Gene expression was studied by real-time PCR and protein detection by immunohistochemistry. Serum testosterone was quantified by RIA. Results showed that EG-VEGF is expressed predominantly in pancreatic islets and vascular endothelium, as well as in RINm5F cells. EG-VEGF gene expression was lower in the pancreas of rats with higher testosterone serum levels. A similar effect that was reverted by flutamide was observed in testosterone-treated RINm5F cells. In summary, testosterone down-regulated EG-VEGF gene expression in rat pancreatic tissue and RINm5F cells. This effect could be mediated by the androgen receptor. To our knowledge, this is the first time that a direct effect of testosterone on EG-VEGF gene expression in rat pancreas and RINm5F cells is demonstrated.
Morales
Angélica
A
Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Vasco de Quiroga # 15 Tlalpan, 14000 México DF, Mexico. amorales@quetzal.innsz.mx
Morimoto
Sumiko
S
Díaz
Lorenza
L
Robles
Guillermo
G
Díaz-Sánchez
Vicente
V
D000818:Animals; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000097:blood / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000235:genetics*
D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D013739:Testosterone