Retinoic acid inhibits human thyroid peroxidase and thyroglobulin gene expression in cultured human thyrocytes.
The effect of retinoic acid (RA) on thyroid peroxidase (TPO) and thyroglobulin (Tg) gene expression was investigated in cultured human thyrocytes. Thyrocytes dispersed from Graves' thyroid tissues were incubated with TSH 5mU/ml and RA 0, 0.01, 0.1, 1.0 microM for 72 h respectively. The samples were then subjected to Northern gel analysis. Northern gel analysis using the specific cDNA probes showed that RA suppressed the accumulation of TPO and Tg mRNA stimulated by TSH in a time- and dose-responsive manner. Furthermore, RA inhibited forskolin and 8-Bromo-cyclic-AMP-induced TPO and Tg gene expression, suggesting a distal action site for these cAMP mediated gene expressions. Immunoprecipitation analysis using the specific monoclonal antibodies showed that TSH increased newly synthesized 100, 75, 36-kDa [35S] TPO. The increased de novo TPO was markedly inhibited by RA. Tg secretion from monolayer cultures was measured by radioimmunoassay. RA also inhibited TSH-induced Tg secretion in a dose dependent manner. RA did not affect [3H] thymidine uptake into primary cultured human thyrocytes. In conclusion, RA inhibits the synthesis of TPO and Tg via the suppression of thyroid-specific gene expression although the exact site of RA action on these genes in human thyroids remains to be further elucidated. These results suggest that RA may play a regulatory role in Tg and TPO gene expression, subsequently resulting in the suppression of thyroid hormone synthesis.
Namba
H
H
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Yamashita
S
S
Morita
S
S
Villadolid
M C
MC
Kimura
H
H
Yokoyama
N
N
Izumi
M
M
Ishikawa
N
N
Ito
K
K
Nagataki
S
S
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D015152:Blotting, Northern; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D015342:DNA Probes; D015870:Gene Expression / Q000187:drug effects*; D006111:Graves Disease / Q000378:metabolism; D006801:Humans; D007163:Immunosorbent Techniques; D007453:Iodide Peroxidase / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D013954:Thyroglobulin / Q000096:biosynthesis / Q000235:genetics*; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*
D015342:DNA Probes; D012333:RNA, Messenger; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D014212:Tretinoin; D013972:Thyrotropin; D004247:DNA; D013954:Thyroglobulin; D007453:Iodide Peroxidase