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    Effects of fibroblast growth factor on type I 5'-deiodinase in FRTL-5 rat thyroid cells

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    Authors
    Tang, Kam-Tsun
    Braverman, Lewis E.
    DeVito, William J.
    UMass Chan Affiliations
    Division of Endocrinology
    Document Type
    Journal Article
    Publication Date
    1994-08-01
    Keywords
    Animals
    Bucladesine
    Cell Line
    Chromatography, High Pressure Liquid
    Cyclic AMP
    Fibroblast Growth Factor 1
    Fibroblast Growth Factor 2
    Forskolin
    Humans
    Iodide Peroxidase
    Kinetics
    RNA, Messenger
    Rats
    Thyroid Gland
    Thyrotropin
    Triiodothyronine, Reverse
    Life Sciences
    Medicine and Health Sciences
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    Link to Full Text
    https://doi.org/10.1210/endo.135.2.7518381
    Abstract
    In the present study, we used FRTL-5 cells to study the effects of fibroblast growth factors (FGFs) on 5'-deiodinase (5'D) activity and messenger RNA (mRNA) levels. In FRTL-5 cells deprived of TSH for 7 days, type I 5'-deiodinase (5'D-I) activity decreased to low, but detectable levels. Incubation of cells with acidic and basic FGFs significantly decreased 5'D-I activity below the basal levels. After 7 days of TSH deprivation, the addition of TSH (100 microU/ml) to the medium for 3 days resulted in an increase in 5'D-I activity. This TSH-induced increase in 5'D-I activity was blocked by the FGFs in a dose-dependent manner. Kinetic analysis revealed that both acidic and basic FGFs decreased the maximum velocity of 5'D-I activity in the presence or absence of TSH, without any significant effect on the Km of enzyme binding. HPLC analysis of the products of the 5'D-I assay revealed that there was no sequential deiodination of rT3. Incubation of FRTL-5 cells with acidic or basic FGF did not affect basal cAMP concentrations, nor did they block the TSH-induced rise in cAMP. However, acidic and basic FGFs inhibited forskolin- and (Bu)2cAMP-induced increases in 5'D-I activity. Incubation of FRTL-5 cells with TSH, (Bu)2cAMP, and forskolin increased 5'D-I mRNA levels. Incubation of FRTL-5 cells with acidic and basic FGFs decreased steady state 5'D-I mRNA levels and blocked the TSH-, forskolin-, and (Bu)2cAMP-induced increases in 5'D-I mRNA. In conclusion, we have demonstrated that FGFs inhibit 5'D-I activity and mRNA levels in FRTL-5 cells in the presence or absence of TSH. The inhibitory effect of FGFs on 5'D-I in FRTL-5 cells is mediated through either a cAMP-independent pathway or pathways distal to the generation of cAMP. The present data together with the identification of FGF in the thyroid gland suggest that FGF may play a physiological role in the regulation of thyroid hormone secretion.
    Source

    Endocrinology. 1994 Aug;135(2):493-500.

    DOI
    10.1210/endo.135.2.7518381
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/42162
    PubMed ID
    7518381
    Related Resources

    Link to Article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1210/endo.135.2.7518381
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