Iodine is crucial for growth and development. Given that persistent iodine imbalance impairs thyroid function and can trigger various pathologies, this study preliminarily investigated the effects and underlying mechanisms of long-term iodine deficiency or excess on thyroid proliferation in rats. We established rat models of iodine deficiency and excess through long-term intervention with a low-iodine diet and deionized water containing different concentrations of potassium iodide. Our results revealed distinct molecular profiles under these conditions: iodine deficiency significantly upregulated the expression of TSHR and PKA-cat, whereas long-term iodine excess markedly suppressed them. Despite these divergent signaling initiations, both conditions resulted in a significant increase in the protein expression of PCNA and Pax8, unequivocally indicating enhanced thyroid follicular cell proliferation. Furthermore, key nodes of the Ras/MAPK pathway, RAS and BRAF, demonstrated a clear upward trend in the late intervention phase in both groups. These findings collectively demonstrate that both iodine deficiency and excess can promote thyroid proliferation; however, the mechanisms involved in driving this proliferative response are likely distinct. Deficiency acts by activating the TSH-TSHR-PKA pathway and synergistically enhancing RAS/BRAF signaling. In contrast, long-term iodine excess promotes thyroid proliferation by enhancing RAS/BRAF activation through inhibition of the TSHR-PKA axis.
Cheng et al. (Fri,) studied this question.