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dc.contributor.authorTang, Kam-Tsun
dc.contributor.authorBraverman, Lewis E.
dc.contributor.authorDeVito, William J.
dc.date2022-08-11T08:10:02.000
dc.date.accessioned2022-08-23T16:52:57Z
dc.date.available2022-08-23T16:52:57Z
dc.date.issued1994-08-01
dc.date.submitted2008-07-09
dc.identifier.citation<p>Endocrinology. 1994 Aug;135(2):493-500.</p>
dc.identifier.issn0013-7227 (Print)
dc.identifier.doi10.1210/endo.135.2.7518381
dc.identifier.pmid7518381
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42162
dc.description.abstractIn 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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=7518381&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1210/endo.135.2.7518381
dc.subjectAnimals
dc.subjectBucladesine
dc.subjectCell Line
dc.subjectChromatography, High Pressure Liquid
dc.subjectCyclic AMP
dc.subjectFibroblast Growth Factor 1
dc.subjectFibroblast Growth Factor 2
dc.subjectForskolin
dc.subjectHumans
dc.subjectIodide Peroxidase
dc.subjectKinetics
dc.subjectRNA, Messenger
dc.subjectRats
dc.subjectThyroid Gland
dc.subjectThyrotropin
dc.subjectTriiodothyronine, Reverse
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleEffects of fibroblast growth factor on type I 5'-deiodinase in FRTL-5 rat thyroid cells
dc.typeJournal Article
dc.source.journaltitleEndocrinology
dc.source.volume135
dc.source.issue2
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/534
dc.identifier.contextkey545016
html.description.abstract<p>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.</p>
dc.identifier.submissionpathoapubs/534
dc.contributor.departmentDivision of Endocrinology
dc.source.pages493-500


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