Regulation of type III iodothyronine deiodinase expression in human cell lines
- PMID: 16935842
- DOI: 10.1210/en.2006-0590
Regulation of type III iodothyronine deiodinase expression in human cell lines
Abstract
Type I iodothyronine deiodinase (D1) and type II iodothyronine deiodinase (D2) catalyze the activation of the prohormone T4 to the active hormone T3; type III iodothyronine deiodinase (D3) catalyzes the inactivation of T4 and T3. D3 is highly expressed in brain, placenta, pregnant uterus, and fetal tissues and plays an important role in regulating thyroid hormone bioavailability during fetal development. We examined the activity of the different deiodinases in human cell lines and investigated the regulation of D3 activity and mRNA expression in these cell lines, as well as its possible coexpression with neighboring genes Dlk1 and Dio3os, which may also be especially important during development. D1 activity and mRNA were only found in HepG2 hepatocarcinoma cells, and D2 activity was observed in none of the cell lines. D3 activity and mRNA was found in ECC-1 endometrium carcinoma cells, MCF-7 mammacarcinoma cells, WRL-68 embryonic liver cells, and SH-SY5Y neuroblastoma cells, but not in the HepG2 hepatocarcinoma cell line or in any choriocarcinoma or astrocytoma cell line. We demonstrated that the phorbol ester 12-O-tetradecanoylphorbol-13-acetate increased D3 activity 2- to 9-fold in ECC-1, MCF-7, WRL-68, and SH-SY5Y cells. Estradiol increased D3 activity 3-fold in ECC-1, but not in any other cells. Dexamethasone decreased D3 activity in WRL-68 cells only in the absence of fetal calf serum. Incubation with retinoids increased D3 activity 2- to 3-fold in ECC-1, WRL-68, and MCF-7 cells but decreased D3 activity in SH-SY5Y cells. D3 expression in the different cells was not affected by cAMP or thyroid hormone. Interestingly, D3 mRNA expression in the different cell lines strongly correlated with Dio3os mRNA expression and in a large set of neuroblastoma cell lines also with Dlk1 expression. In conclusion, we identified different human D3-expressing cell lines, in which the regulation of D3 expression is cell type-specific. Our data suggest that estradiol may be one of the factors contributing to the induction of D3 activity in the pregnant uterus and that in addition to gene-specific regulatory elements, more distant common regulatory elements also may be involved in the regulation of D3 expression.
Similar articles
-
Glucagon-like peptide-1 stimulates type 3 iodothyronine deiodinase expression in a mouse insulinoma cell line.Life Sci. 2014 Oct 12;115(1-2):22-8. doi: 10.1016/j.lfs.2014.09.004. Epub 2014 Sep 21. Life Sci. 2014. PMID: 25241124
-
Large induction of type III deiodinase expression after partial hepatectomy in the regenerating mouse and rat liver.Endocrinology. 2009 Jan;150(1):540-5. doi: 10.1210/en.2008-0344. Epub 2008 Sep 11. Endocrinology. 2009. PMID: 18787028
-
Regulation of thyroid hormone metabolism during fetal development.Mol Cell Endocrinol. 1999 May 25;151(1-2):37-47. doi: 10.1016/s0303-7207(99)00088-x. Mol Cell Endocrinol. 1999. PMID: 10411318 Review.
-
Expression profiles of the three iodothyronine deiodinases, D1, D2, and D3, in the developing rat.Endocrinology. 1999 Feb;140(2):844-51. doi: 10.1210/endo.140.2.6537. Endocrinology. 1999. PMID: 9927314
-
Thyroid hormone deiodinases--a selenoenzyme family acting as gate keepers to thyroid hormone action.Acta Med Austriaca. 1996;23(1-2):17-30. Acta Med Austriaca. 1996. PMID: 8767511 Review.
Cited by
-
Mice lacking DIO3 exhibit sex-specific alterations in circadian patterns of corticosterone and gene expression in metabolic tissues.BMC Mol Cell Biol. 2024 Mar 29;25(1):11. doi: 10.1186/s12860-024-00508-6. BMC Mol Cell Biol. 2024. PMID: 38553695 Free PMC article.
-
The impact of vitamin A supplementation on thyroid function and insulin sensitivity: implication of deiodinases and phosphoenolpyruvate carboxykinase in male Wistar rats.Eur J Nutr. 2022 Dec;61(8):4091-4105. doi: 10.1007/s00394-022-02945-5. Epub 2022 Jul 9. Eur J Nutr. 2022. PMID: 35804266 Free PMC article.
-
Deiodinases and Cancer.Endocrinology. 2021 Apr 1;162(4):bqab016. doi: 10.1210/endocr/bqab016. Endocrinology. 2021. PMID: 33539515 Free PMC article. Review.
-
Decreased expression of the thyroid hormone-inactivating enzyme type 3 deiodinase is associated with lower survival rates in breast cancer.Sci Rep. 2020 Aug 17;10(1):13914. doi: 10.1038/s41598-020-70892-4. Sci Rep. 2020. PMID: 32807826 Free PMC article.
-
Regulation of type 3 deiodinase in rodent liver and adipose tissue during fasting.Endocr Connect. 2020 Jun;9(6):552-562. doi: 10.1530/EC-20-0189. Endocr Connect. 2020. PMID: 32449699 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources