Leptin regulation of the thyroids: negative regulation on thyroid hormone levels in euthyroid subjects and inhibitory effects on iodide uptake and Na+/I- symporter mRNA expression in rat FRTL-5 cells.
Leptin receptors are distributed throughout the body and leptin has been shown to have various effects. As we have recently demonstrated a positive correlation between serum leptin levels and TSH in euthyroid subjects, we investigated the effect of leptin on the thyroids. It was observed that serum leptin levels were negatively correlated with free thyroxine/TSH ratios in the serum of euthyroid female subjects. This suggests that leptin may modulate TSH effects. RT-PCR for leptin receptor expression revealed that FRTL-5 cells possess the gene transcript to the long cytoplasmic form of the receptor. Leptin actually appeared to induce an increase in c-fos mRNA expression. However, it inhibited iodide uptake typically induced by both TSH and dibutyryl cAMP, while leptin did not inhibit TSH-induced cAMP production or TSH-stimulated DNA synthesis in 4H medium (in the absence of insulin and TSH). Leptin also was observed to inhibit TSH- and dibutyryl cAMP-induced Na+/I- symporter and thyroglobulin mRNA expression. Lastly, leptin was seen to inhibit TSH-stimulated thymidine incorporation in 5H medium. Taken together, these results suggest that leptin suppresses TSH-induced thyroid function. Therefore, we hypothesized that leptin may be one of the regulators of thyroid function in obese patients.
Isozaki
Osamu
O
Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical University, Japan.
Tsushima
Toshio
T
Nozoe
Yasuko
Y
Miyakawa
Megumi
M
Takano
Kazue
K
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos / Q000235:genetics; D006801:Humans; D007454:Iodides / Q000378:metabolism*; D020738:Leptin / Q000097:blood / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics; D054411:Receptors, Leptin; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000235:genetics*; D013954:Thyroglobulin / Q000235:genetics; D013961:Thyroid Gland / Q000737:chemistry / Q000378:metabolism*; D013963:Thyroid Hormones / Q000097:blood*; D013972:Thyrotropin / Q000097:blood / Q000494:pharmacology; D013974:Thyroxine / Q000097:blood; D000099209:Sodium-Iodide Symporters
D003994:Bucladesine; D000242:Cyclic AMP; D004247:DNA; D007454:Iodides; D020738:Leptin; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins; D027981:Symporters; D013954:Thyroglobulin; D013963:Thyroid Hormones; D013972:Thyrotropin; D013974:Thyroxine; D000099209:Sodium-Iodide Symporters; C515448:LEPR protein, human