Study of the molecular basis of the short-term regulation of the Na+/I- symporter (NIS) and pendrin gene expression in rats thyroid and PCCl3 cells: possible contribution to the comprehension of the Wolff-Chaikoff effect and the escape phenomenon

• Grant number: 09/17834-6
• Support Opportunities: Regular Research Grants
• Duration: July 01, 2010 - June 30, 2012
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Tereza Nunes
• Grantee: Maria Tereza Nunes
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Iodine is essential for the thyroid hormones (TH) synthesis. Its uptake occurs via the Na+/I- Symporter (NIS), and its efflux to the follicular lumen, where it is oxidized and organified, occurs via Pendrina, a protein expressed along the apical plasma membrane of the thyrocytes. However, it is known that the chronic ingestion of high doses of iodide can be harmful for thyroid function, being a frequent cause of hypothyroidism. It is also known that the acute ingestion of high doses of iodide leads to a blockade of TH synthesis, which is known as the Wolff-Chaikoff effect. This effect is followed by an escape phenomenon within ~48h, which leads the thyroid to recover its functional activity. These events constitute a high specialized mechanism for the thyroid autoregulation process, which protect it from the deleterious effects of the iodide excess. However, little is known about the molecular mechanisms involved in these phenomena. It is known that the excess of iodide reduces NIS expression, which might decrease its thyroidal content at levels that the Wolff-Chaikoff effect could not be sustained. In fact, we have demonstrated that iodide per se reduces NIS mRNA expression and polyadenylation, in short periods of time (30 min to 24 h), which would protect the thyroid from its excess. Preliminary studies from our laboratory also indicated that the excess of iodide increases the pendrin mRNA expression, which might increase its efflux to the follicular lumen, indicating a novel possibility by which the thyroid could escape from the Wolff-Chaikoff effect. The present study aimed to investigate the molecular basis involved in the Wolff-Chaikoff effect and its escape, by evaluating the regulation of NIS and Pendrin gene expression by the excess of iodide, at transcriptional and posttranscriptional level. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SERRANO-NASCIMENTO, CAROLINE; TEIXEIRA, SILVANIA DA SILVA; PABLO NICOLA, JUAN; NACHBAR, RENATO TADEU; MARIA MASINI-REPISO, ANA; NUNES, MARIA TEREZA. The Acute Inhibitory Effect of Iodide Excess on Sodium/Iodide Symporter Expression and Activity Involves the PI3K/Akt Signaling Pathway. Endocrinology, v. 155, n. 3, p. 1145-1156, MAR 2014. (09/17834-6)

SERRANO-NASCIMENTO, CAROLINE; CALIL-SILVEIRA, JAMILE; GOULART-SILVA, FRANCEMILSON; NUNES, MARIA TEREZA. New insights about the posttranscriptional mechanisms triggered by iodide excess on sodium/iodide symporter (NIS) expression in PCCl3 cells. Molecular and Cellular Endocrinology, v. 349, n. 2, p. 154-161, FEB 26 2012. (10/05503-2, 09/17834-6)

CALIL-SILVEIRA, JAMILE; SERRANO-NASCIMENTO, CAROLINE; KOPP, PETER ANDREAS; NUNES, MARIA TEREZA. Iodide excess regulates its own efflux: a possible involvement of pendrin. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, v. 310, n. 7, p. C576-C582, APR 1 2016. (12/24391-6, 10/05503-2, 09/17834-6, 12/13011-8)

SERRANO-NASCIMENTO, CAROLINE; PABLO NICOLA, JUAN; TEIXEIRA, SILVANIA DA SILVA; POYARES, LEONICE LOURENCO; LELLIS-SANTOS, CAMILO; BORDIN, SILVANA; MARIA MASINI-REPISO, ANA; NUNES, MARIA TEREZA. Excess iodide downregulates Na+/I- symporter gene transcription through activation of PI3K/Akt pathway. Molecular and Cellular Endocrinology, v. 426, n. C, p. 73-90, MAY 5 2016. (09/17834-6)