EXPRESSION OF THE ENDOTHELIN-1 GENE IN THE RAT-THYROID GLAND AND CHANGES IN ITS PEPTIDE AND MESSENGER-RNA LEVELS IN GOITER FORMATION AND IODIDE-INDUCED INVOLUTION

Endothelin-1 (ET-1) is a major vasoconstrictor peptide, first found in endothelial cells, and later in many other tissues, including the thy roid gland. We analysed the expression of the ET-1 gene in the rat thy roid gland and changes in ET-1 mRNA and peptide levels in goiter devel opment and involution, two circumstances characterised by vascular cha nges. Thyroid hyperplasia was induced in adult Wistar rats by feeding a low iodine diet (LID) supplemented with 0.25% thiouracil for 10 days , and LID alone for 2 further days (H.12 group). Involution was induce d by injecting 100 mu g iodide and refeeding a normal diet during 6 h, 12 h, and 24 h (I.6 h, I.12 h, I.24 h groups). Rats fed a normal iodi ne diet were used as controls. A specific 488 bp cDNA corresponding to the known sequence of pre-pro ET-1 was found by RT-PCR from RNA extra cts in all thyroid experimental groups, as well as in lung and kidney which were used as positive controls. RP-HPLC analysis showed that ET- 1 immunoreactivity eluted similarly as mature ET-1. During hyperplasia , ET-1 mRNA and peptide levels were increased 3.5- and 5-fold respecti vely. The relative volume of the vascular bed was more than doubled. D uring iodide-induced involution, the glandular ET-1 mRNA level remaine d elevated. The concentration of ET-1 peptide increased and was signif icantly greater at 12 h involution than in the H.12 group. At this tim e, the capillary reticulum reverted to individual capillaries and the vascular bed was significantly reduced. These data demonstrate that th e ET-1 gene is expressed in the rat thyroid gland and that the ET-1 mR NA and peptide levels are increased during thyroid hyperplasia and rem ain elevated during a phase of rapid iodide-induced involution. These data suggest that changes in ET-1 production may play a role in contro l of thyroid gland trophic regulation and vascularity.