1,25-dihydroxyvitamin D3 attenuates TSH and 8-(4-chlorophenylthio)-cAMP-stimulated growth and iodide uptake by rat thyroid cells (FRTL-5).
The effects of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on TSH and the 3',5'-cyclic adenosine monophosphate (cAMP) analogue 8-(4-chlorophenylthio)-cAMP-stimulated cell growth and iodide uptake were studied in a rat thyroid cell line (FRTL-5). 1,25-(OH)2D3 inhibited both TSH and 8-(4-chlorophenylthio)-cAMP-induced cell proliferation with the maximum effect at 100 nmol/L. The inhibitory effect of 1,25-(OH)2D3 (10 nmol/L) on TSH and 8-(4-chlorophenylthio)-cAMP-stimulated iodide uptake was observed after 2 days of incubation, and the effect was maximal after 4 days. The inhibition was dose-dependent and maximal at 100 nmol/L 1,25-(OH)2D3. 1,25-(OH)2D3 (10 nmol/L, 4 days) increased the median concentrations of TSH required to stimulate both cAMP production and iodide uptake half-maximally by 124 and 187%, respectively, whereas the median 8-(4-chlorophenylthio)-cAMP concentration was not changed. Lineweaver-Burke plots revealed that 1,25-(OH)2D3 reduced the Vmax of the sodium-driven iodide carriers to 30% of the control cells without effect on the Km. Iodide efflux was only slightly increased in the 1,25-(OH)2D3-treated cells. In conclusion, 1,25-(OH)2D3 potently inhibited the TSH-stimulated growth and iodide uptake by FRTL-5 cells both by reducing the TSH-stimulated cAMP production and by attenuating the stimulatory effects of cAMP.
Berg
J P
JP
Hormone Laboratory, Aker Hospital, Oslo, Norway.
Torjesen
P A
PA
Haug
E
E
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007454:Iodides / Q000378:metabolism*; D007700:Kinetics; D051381:Rats; D013873:Thionucleotides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013972:Thyrotropin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013997:Time Factors
D007454:Iodides; D013873:Thionucleotides; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D013972:Thyrotropin; D000242:Cyclic AMP; D002117:Calcitriol