Increased expression of endothelin‐1 converting enzyme in human thyroid carcinoma

Endothelin-l (ET-l), a 21amino-acid peptide possessing vasoconstrictive and mitogenic properties, is principally released by the vascular endothelium (Yanagisawa et al., 1988; Donckier et al., 1991) but can also be produced by thyroid follicular cells (Lenziardi et al. 1995). In the September 2003 issue of Clinical Endocrinology, we demonstrated that both ET-1 mRNA and ET-l peptide as well as the effector receptor ETAR mRNA levels were increased in thyroid papillary carcinoma and Hashimoto's thyroiditis (Donckier et al., 2003). ET-1 peptide is synthesized through successive proteolytic cleavage of a 203-amino-acid precursor to obtain Big-endothelin-1 (1-38Big-ET-l). During secretion, 1-38Big-ET-l is cleaved by a specific membrane-bound metalloproteinase, the ET-l converting enzyme (ECE-1) that leads to the equimolar secretion of the ET-1 active form (1-21ET-1) and the C-terminal fragment (22-38CTF or 22-38Big-ET-1) (Kido et al., 1997). The physiological importance of this cleavage is indicated by the reported 140-fold increase in vasoconstrictor potency upon cleavage to 1-21ET-l (Kimura et al., 1989). Because the amounts of cross-reactivity from our anti-ET-l antibody were 100%, 87% and 0%, respectively, for 1-21ET-1, 1-38Big-ET-l and 22-38CTF, our study suggested that the increased ET-l immunostaining, as evaluated by counting the number of positive cells among 1000 follicular cells, may result from mixed labelling of 1-21ET-1 and 1-38Big-ET-l. In this respect, we considered it of importance to demonstrate that increased expression of the ET-1 peptide could be related to an increased expression of the ECE-l.