Submitted on October 30, 2008
Revised on February 13, 2009
Accepted on March 24, 2009
Iodide deficiency-induced angiogenic stimulus in the thyroid occurs via HIF- and reactive oxygen species (ROS)-dependent VEGF-A secretion from thyrocytes
Anne-Catherine Gerard1*, Sylvie Poncin1, Jean-Nicolas Audinot2, Jean-François Denef1, and Ides Colin1
1 Universite catholique de Louvain
2 Centre de Recherche Gabriel
* To whom correspondence should be addressed. E-mail: anne-catherine.gerard{at}uclouvain.be.
Vascular supply is an obvious requirement for all organs. In addition to oxygen and nutrients, blood flow also transports essential trace elements. Iodine, which is a key element in thyroid hormone synthesis, is one of them. An inverse relationship exists between the expansion of the thyroid microvasculature and the local availability of iodine. This microvascular trace element-dependent regulation is unique and contributes to keep steady the iodide delivery to the thyroid. Signals involved in this regulation, such as VEGF-A, originate from thyrocytes as early TSH-independent responses to iodide scarcity. The question raised in this paper is how thyrocytes, facing an acute drop in intracellular stores of iodine; generate angiogenic signals acting on adjacent capillaries. Using in vitro models of rat and human thyroid cells, we show for the first time that the deficit in iodine, is related to the release of VEGF-A via a reactive oxygen species/hypoxia inducible factor-1-dependent pathway.
