Endocrine gland-derived vascular endothelial growth factor in rat pancreas: genetic expression and testosterone regulation

Abstract

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 realtime 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.

Endocrine gland-derived vascular endothelial growth factor modulates proliferation, apoptosis and migration in pancreatic cancer cells

“…Notably, the expression of EG-VEGF was also detected in the normal pancreatic islets. This phenomenon has also been observed in other studies (13,14). The positive expression of the EG-VEGF in the normal pancreatic islets suggests a function for EG-VEGF in the mediation of endocrine function.…”

Sex steroids effects on the endocrine pancreas

“…We found that testosterone down-regulates the mRNA of EG-VEGF in a dose response fashion, and the treatment with flutamide revert the effect [87]. The role of EG-VEGF in pancreas has not yet been completely established but in other steroidogenics cells and tissues, induces the proliferation, migration, and fenestration of endothelial cells, and has also been shown to act as survival factor modulating the growth of certain cells [88], it might be plausible then, that EG-VEGF produces similar effects in the pancreas.…”

Therapeutic Potential of Targeting Prokineticin Receptors in Diseases

“…Since human pancreatic cells have steroidogenic activity, PK1 has been found to be expressed not only in normal pancreas but also in pancreatic adenocarcinoma (PC), where it is upregulated in islet cells, mainly in males, in the exocrine part, mainly in females, and in the blood vessels (Morales et al, 2007(Morales et al, , 2008. PC is characterized by poor vascularization and the presence of a large number of myeloid cells (Korc, 2007).…”