Effects of fibroblast growth factor on type I 5'-deiodinase in FRTL-5 rat thyroid cells.
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.
Tang
K T
KT
Division of Endocrinology, University of Massachusetts Medical Center, Worcester 01655.
Braverman
L E
LE
DeVito
W J
WJ
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013961:Thyroid Gland / Q000187:drug effects / Q000201:enzymology*; D013972:Thyrotropin / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology; D014285:Triiodothyronine, Reverse / Q000378:metabolism
D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D005576:Colforsin; D014285:Triiodothyronine, Reverse; D003994:Bucladesine; D013972:Thyrotropin; D000242:Cyclic AMP; D007453:Iodide Peroxidase