ArticleProceedings of the National Academy of Sciences of the United States of America2003
Preferential megalin-mediated transcytosis of low-hormonogenic thyroglobulin: a control mechanism for thyroid hormone release.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 58 citations in OpenAlex.
- Failure to use measurement of megalin secretory components complexed with serum thyroglobulin as a tool to identify metastases after surgery in papillary thyroid cancer.Journal of endocrinological investigationTrial
- Receptor-mediated endocytosis by Megalin: Exploring its role in ligand interaction and disease mechanisms.Genes & diseases · 2026Review
- Pragmatic Use of Thyroid Autoantibodies in Clinical Practice: An Update.TouchREVIEWS in endocrinology · 2026Review
- Substrate for Thyroid Hormone Synthesis: Biochemistry, Evolution, and Physiology.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Protein handling in kidney tubules.Nature reviews. Nephrology · 2025Review
- Perfluorooctanesulfonic acid (PFOS) disrupts cadherin-16 in the developing rat thyroid gland.Current research in toxicology · 2024Article
- Normal and Sjogren's syndrome models of the murine lacrimal gland studied at single-cell resolution.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Usefulness of Thyroid Antibodies in the Diagnostic Approach to Autoimmune Thyroid Disease.Antibodies (Basel, Switzerland) · 2023Review
- A glance at post-translational modifications of human thyroglobulin: potential impact on function and pathogenesis.European thyroid journal · 2022Review
- Cryo-EM: A new dawn in thyroid biology.Molecular and cellular endocrinology · 2021Review
- Prediction of heparin binding of mutated short sequences of rat thyroglobulin.Journal of endocrinological investigation · 2021Article
- The role of thyroglobulin in thyroid hormonogenesis.Nature reviews. Endocrinology · 2019Review
- Fluoride Exposure Induces Inhibition of Sodium/Iodide Symporter (NIS) Contributing to Impaired Iodine Absorption and Iodine Deficiency: Molecular Mechanisms of Inhibition and Implications for Public Health.International journal of environmental research and public health · 2019Review
- Vitamin D Binding Protein: A Historic Overview.Frontiers in endocrinology · 2019Review
- Binding of thyroglobulin (Tg) to the low-density lipoprotein receptor-associated protein (RAP) during the biosynthetic pathway prevents premature Tg interactions with sortilin.Journal of endocrinological investigation · 2017Article
- Intracellular retention of thyroglobulin in the absence of the low-density lipoprotein receptor-associated protein (RAP) is likely due to premature binding to megalin in the biosynthetic pathway.Journal of endocrinological investigation · 2016Article
- Recent insights into the cell biology of thyroid angiofollicular units.Endocrine reviews · 2013Review
- The Vps10p-domain receptor family.Cellular and molecular life sciences : CMLS · 2009Review
- The role of the placenta in thyroid hormone delivery to the fetus.Nature clinical practice. Endocrinology & metabolism · 2009Review
- Kidney abnormalities in low density lipoprotein receptor associated protein knockout mice.Journal of endocrinological investigation · 2008Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Hormone secretion by thyrocytes occurs by fluid phase uptake and lysosomal degradation of the prohormone thyroglobulin (Tg). However, some Tg internalized by megalin bypasses lysosomes and is transcytosed across cells and released into the bloodstream. Because the hormone content of Tg is variable, we investigated whether this affects transcytosis. We found that rat Tg with a low hormone content [low-hormonogenic rat Tg (low-horm-rTg)] is transcytosed by megalin across thyroid FRTL-5 cells to a greater extent than rat Tg with a high hormone content [hormonogenic rat Tg (horm-rTg)]. In immunoprecipitation experiments, the Tg sequence Arg-2489-Lys-2503 (required for binding to megalin and heparan sulfate proteoglycans) was found to be more exposed in low-horm-rTg, which accounted for its preferential transcytosis. Thus, removal of surface heparan sulfate proteoglycans from FRTL-5 cells or blocking of 2489-2503 reduced transcytosis of low-horm-rTg to a greater extent than that of horm-rTg. Preferential transcytosis of low-horm-rTg affected hormone release. Thus, the increase in hormone release from horm-rTg in FRTL-5 cells determined by megalin blocking (due to reduced transcytosis and enhanced Tg degradation) was rescued by low-horm-rTg, suggesting that megalin is required for effective hormone release. This finding was confirmed in a small number of megalin-deficient mice, which had serological features resembling mild hypothyroidism. Reduced hormone formation within Tg in vivo, due to treatment of rats with aminotriazole or of patients with Graves' disease with methimazole, resulted in increased Tg transcytosis via megalin, in confirmation of results with FRTL-5 cells. Our study points to a major role of megalin in thyroid homeostasis with possible implications in thyroid diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.