IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
The role of GnRH analogues in endometriosis-associated apoptosis and angiogenesis.
Autor/es:
TESONE M, BILOTAS M, BARAÑAO RI, MERESMAN G
Revista:
Gynecol Obstet Invest
Editorial:
S. Karger AG, Basel
Referencias:
Año: 2008 vol. 66 p. 10 - 18
Resumen:
It has been postulated that gonadotropin-releasing hormone
(GnRH) analogues may act directly on endometrial
cells and inhibit their growth and proliferation by regulation
of apoptotic and angiogenic mechanisms. Eutopic endometrial
cells from patients with endometriosis show an increased
proliferation rate and are less susceptible to cell
death by apoptosis than those from subjects without the disease.
Notably, the GnRH analogue, leuprorelin, inhibits cell
proliferation and increases the apoptotic rate in eutopic endometrial
cell cultures, an effect that appears to be mediated
by an increase in the expression of the pro-apoptotic proteins
Bax and FasL and a decrease in the expression of the
anti-apoptotic protein Bcl-2. Angiogenesis is an important
process in the development of endometrial tissue, and it is
regulated by vascular endothelial growth factors (VEGFs)
and angiopoietins. VEGF levels are elevated in peritoneal fluid
and endometriotic tissue from patients with endometriosis.
In addition, it has been demonstrated that the expression
of VEGF is potentiated by a variety of cytokines,
including IL-1 _ . Recent studies show that leuprorelin reduces
the production of VEGF-A and IL-1 _ in eutopic endometrial
cell cultures, suggesting a mechanism by which it could inhibit the development of endometriosis. Thus, GnRH analogues
appear to be effective in reducing the growth of endometrial
cells, not only due to their classical pituitary endocrine
effects, but also via a direct effect on the endometrial
cells themselves.