TSH regulates pendrin membrane abundance and enhances iodide efflux in thyroid cells

Endocrinology. 2012 Jan;153(1):512-21. doi: 10.1210/en.2011-1548. Epub 2011 Nov 22.

Abstract

Thyroid hormones are essential for normal development and metabolism. Their synthesis requires transport of iodide into thyroid follicles. The mechanisms involving the apical efflux of iodide into the follicular lumen are poorly elucidated. The discovery of mutations in the SLC26A4 gene in patients with Pendred syndrome (congenital deafness, goiter, and defective iodide organification) suggested a possible role for the encoded protein, pendrin, as an apical iodide transporter. We determined whether TSH regulates pendrin abundance at the plasma membrane and whether this influences iodide efflux. Results of immunoblot and immunofluorescence experiments reveal that TSH and forskolin rapidly increase pendrin abundance at the plasma membrane through the protein kinase A pathway in PCCL-3 rat thyroid cells. The increase in pendrin membrane abundance correlates with a decrease in intracellular iodide as determined by measuring intracellular (125)iodide and can be inhibited by specific blocking of pendrin. Elimination of the putative protein kinase A phosphorylation site T717A results in a diminished translocation to the membrane in response to forskolin. These results demonstrate that pendrin translocates to the membrane in response to TSH and suggest that it may have a physiological role in apical iodide transport and thyroid hormone synthesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Membrane / metabolism
  • Chloride-Bicarbonate Antiporters / genetics
  • Chloride-Bicarbonate Antiporters / metabolism*
  • Colforsin / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Goiter, Nodular / genetics
  • Goiter, Nodular / metabolism
  • Hearing Loss, Sensorineural / genetics
  • Hearing Loss, Sensorineural / metabolism
  • Humans
  • Iodides / metabolism*
  • Ion Transport / drug effects
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Rats
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • Sulfate Transporters
  • Thyroid Gland / drug effects*
  • Thyroid Gland / metabolism*
  • Thyrotropin / metabolism
  • Thyrotropin / pharmacology*

Substances

  • Chloride-Bicarbonate Antiporters
  • Iodides
  • Membrane Transport Proteins
  • Recombinant Proteins
  • SLC26A4 protein, human
  • Slc26A4 protein, rat
  • Sulfate Transporters
  • Colforsin
  • Thyrotropin
  • Cyclic AMP-Dependent Protein Kinases

Supplementary concepts

  • Pendred syndrome
pFad - Phonifier reborn

Pfad - The Proxy pFad of © 2024 Garber Painting. All rights reserved.

Note: This service is not intended for secure transactions such as banking, social media, email, or purchasing. Use at your own risk. We assume no liability whatsoever for broken pages.


Alternative Proxies:

Alternative Proxy

pFad Proxy

pFad v3 Proxy

pFad v4 Proxy