Effects of fibroblast growth factor on type I 5'-deiodinase in FRTL-5 rat thyroid cells
dc.contributor.author | Tang, Kam-Tsun | |
dc.contributor.author | Braverman, Lewis E. | |
dc.contributor.author | DeVito, William J. | |
dc.date | 2022-08-11T08:10:02.000 | |
dc.date.accessioned | 2022-08-23T16:52:57Z | |
dc.date.available | 2022-08-23T16:52:57Z | |
dc.date.issued | 1994-08-01 | |
dc.date.submitted | 2008-07-09 | |
dc.identifier.citation | <p>Endocrinology. 1994 Aug;135(2):493-500.</p> | |
dc.identifier.issn | 0013-7227 (Print) | |
dc.identifier.doi | 10.1210/endo.135.2.7518381 | |
dc.identifier.pmid | 7518381 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/42162 | |
dc.description.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. | |
dc.language.iso | en_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.url | https://doi.org/10.1210/endo.135.2.7518381 | |
dc.subject | Animals | |
dc.subject | Bucladesine | |
dc.subject | Cell Line | |
dc.subject | Chromatography, High Pressure Liquid | |
dc.subject | Cyclic AMP | |
dc.subject | Fibroblast Growth Factor 1 | |
dc.subject | Fibroblast Growth Factor 2 | |
dc.subject | Forskolin | |
dc.subject | Humans | |
dc.subject | Iodide Peroxidase | |
dc.subject | Kinetics | |
dc.subject | RNA, Messenger | |
dc.subject | Rats | |
dc.subject | Thyroid Gland | |
dc.subject | Thyrotropin | |
dc.subject | Triiodothyronine, Reverse | |
dc.subject | Life Sciences | |
dc.subject | Medicine and Health Sciences | |
dc.title | Effects of fibroblast growth factor on type I 5'-deiodinase in FRTL-5 rat thyroid cells | |
dc.type | Journal Article | |
dc.source.journaltitle | Endocrinology | |
dc.source.volume | 135 | |
dc.source.issue | 2 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/oapubs/534 | |
dc.identifier.contextkey | 545016 | |
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.submissionpath | oapubs/534 | |
dc.contributor.department | Division of Endocrinology | |
dc.source.pages | 493-500 |