Inhibition of gap-junctional-intercellular communication in thyroid-follicular cells by propylthiouracil and low iodine diet

Propylthiouracil (PTU) or low-iodine diet (LTD) treatment increases thyroid -follicular-cell proliferation, possibly by disrupting the movement of smal l molecules ( < 1.2 kD) through membrane channels called gap junctions. Num erous tumor promoters and proliferative disease slates exhibit inhibited ga p-junctional-intercellular communication (GJIC) prior to the induction of c ell proliferation, yet the association between CJIC and apoptosis is unclea r. In the present study, we used an ex vivo method to examine whether GJIC is inhibited in the thyroid of PTU- or LID-treated rats. Tn addition, the e ffect of these models of hypothyroidism on thyroid-follicular-cell prolifer ation and apoptosis was examined to determine the association between GJIC and cell homeostasis. After 14 days of treatment of either PTU or LID (plus 1% KClO4 in the drinking water), serum tri-iodothyronine (T-3) and thyroxi ne, (T-4) was decreased to nearly undetectable levels and serum TSH was inc reased in PTU- and LID-treated rats. At the same time point, GJIC was decre ased 30-35% in PTU- and LID-treated rats while thyroid-follicular-cell prol iferation increased nearly threefold in both treatment groups. Interestingl y, apoptosis increased twofold in both hypothyroid treatment groups. These data suggest that PTU or LID treatment inhibit thyroid GJIC during a state of increased thyroid-follicular-cell proliferation and apoptosis. While the increase in proliferation was anticipated, the paradoxical increase in apo ptosis during decreased GJIC in thyroid-follicular cells warrants further e xamination. (C) 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.