Possible Role Of Egvegf In Pathological Conditions

EG-VEGF may have considerable pathophysiological and therapeutic significance for several endocrine disorders characterized by excessive angiogenesis and for certain endocrine gland tumors. We have recently evaluated the expression of EG-VEGF in a panel of human ovary specimens isolated from patients diagnosed with poly-cystic ovary syndrome (PCOS) (N. Ferrara et al., in prep.). This condition is a major cause of infertility, affecting 5-10% of women of reproductive age (Goldziher and Green 1962; Dunaif and Thomas 2001). It is known that the increase in ovary mass in PCOS is accompanied by extensive angiogenesis in the stroma and theca (Yen 1999). Our previous studies have demonstrated that ade-novirus-mediated delivery of EG-VEGF in the ovary elicits an angiogenic response and cyst formation, similar to that induced by VEGF (LeCouter et al. 2001). Although both EG-VEGF and VEGF are expressed in the PCOS ovaries, their expression patterns are very distinct, essentially nonoverlapping. VEGF mRNA expression is associated with the granulosa cell layer. EG-VEGF expression is strongly correlated with the hyperplastic stroma and thecal cells, indicating that this molecule may participate in the hyperplastic/angiogenic changes that occur in PCOS. We propose that, in addition to the potentially coordinating activities that promote angiogene-sis in the normal human ovary, VEGF and EG-VEGF may also jointly contribute to the development of PCOS.

We are currently assessing the expression of EG-VEGF and VEGF in a series of adrenal gland tumor specimens (our unpublished observations). Again, the expression pattern of EG-VEGF is rather distinct from that exhibited by VEGF. In adrenal-medulla-derived tumors (pheochromocytomas), VEGF is highly expressed throughout, whereas EG-VEGF is undetectable. In contrast, carcinomas of cortical origin express both VEGF and EG-VEGF. These data exemplify the concept that therapies to affect therapeutic angiogenesis or antiangio-genesis may require knowledge of the tissue-specific molecules that regulate and maintain the distinct vascular beds. Currently, we are examining the expression and potential role of EG-VEGF in other endocrine disease states, including pathologies of the placenta. The therapeutic values of EG-VEGF neutralizing reagents, and of EG-VEGF receptor-specific agonists or antagonists, remain to be demonstrated.

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