Stimulation of rat atrial natriuretic peptide (rANP) synthesis by triiodothyronine and thyroxine (T4): T4 as a prohormone in synthesizing rANP.
Thyroid hormones have been reported to increase the secretion and synthesis of atrial natriuretic peptide (ANP) in vitro. In this study, we focused on the role of type I T4 5'-deiodinase to investigate the stimulating effects of T4 on ANP synthesis and secretion by measuring cellular content and secretion into the medium of immunoreactive rat ANP (IR-rANP) and rANP mRNA levels in cultured rat neonatal atrial myocytes. Both T3 (10(-9)-10(-7) M) and T4 (10(-8)-10(-6) M) increased cellular content and secretion into the medium of IR-rANP in a dose-dependent manner. However, these effects of T4 were completely inhibited by the addition of propylthiouracil, which selectively suppressed type I T4 5'-deiodinase activity. Methimazole, which did not alter T4 5'-deiodinase activity, had no effects on T4-induced IR-rANP increase. In the measurements of rANP mRNA levels by dot blot analysis, T3 (10(-8) and 10(-7) M) and T4 (10(-7) and 10(-6) M) increased rANP mRNA levels in the same way as they increased IR-rANP content. Although T4-increased rANP mRNA levels were also inhibited by propylthiouracil, methimazole did not alter the effect of T4. Moreover, T4-induced rANP mRNA accumulation in atrial myocytes was further stimulated by the addition of dithiothreitol, suggesting that the deiodinating activity was thiol sensitive. These data suggest that the stimulating effect of T4 on cellular IR-rANP content and rANP mRNA levels is entirely induced after it is converted to T3 by type I T4 5'-deiodinase in atrial myocytes and that T4 serves as a prohormone for T3 in synthesizing rANP.
Mori
Y
Y
Second Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Nishikawa
M
M
Matsubara
H
H
Takagi
T
T
Toyoda
N
N
Oikawa
S
S
Inada
M
M
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D011355:Prodrugs / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011863:Radioimmunoassay; D051381:Rats; D011994:Recombinant Proteins; D013974:Thyroxine / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology*
D011355:Prodrugs; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014284:Triiodothyronine; D009320:Atrial Natriuretic Factor; D013974:Thyroxine