Spiking expression of mu-crystallin mRNA during treatment with methimazole in patients with graves' hyperthyroidism.
mu-Crystallin is an NADPH-dependent cytosolic T3-binding protein. A knockout study in mice showed that mu-crystallin has a physiological function as a reservoir of T3 in the cytoplasm in vivo. Patients with nonsyndromic deafness were reported to have point mutations in the mu-crystallin gene. The expression of mu-crystallin is regulated by multiple factors. The present study was performed to determine whether thyroid function is related to the expression of mu-crystallin mRNA in peripheral mononuclear cells. We examined 23 normal healthy male and female subjects and 15 patients with Graves' disease. mu-Crystallin protein expression was determined immunohistochemically in peripheral mononuclear cells. The expression of mu-crystallin mRNA was assessed by reverse transcription of total RNA from peripheral mononuclear cells followed by quantitative PCR. mu-Crystallin protein was detected in peripheral mononuclear cells. The mRNA expression was negatively correlated with age in normal female subjects. The values in female subjects were significantly higher than those in males. The values were positively correlated with serum TSH concentration. The values of the thyrotoxic patients with Graves' disease were lower than those in healthy subjects. A transient increase in mu-crystallin expression was observed within 14-42 days after the initial treatment with antithyroid medication. Thyroid hormone inversely relates to the expression of mu-crystallin mRNA in euthyroid mononuclear cells. Abrupt suppression of thyroid function leads to overexpression of mu-crystallin mRNA in thyrotoxic mononuclear cells. Thyroid hormone-regulated mu-crystallin expression may control thyroid hormone action via the intracytoplasmic T (3) capacity.
Suzuki
S
S
Department of Aging Medicine and Geriatrics, Institute on Aging and Adaptation, Shinshu University, Graduate School of Medicine, Matsumoto, Japan. suzukis@shinshu-u.ac.jp
Takei
M
M
Nishio
S
S
Inaba
H
H
Sato
A
A
Yamazaki
M
M
Shinomiya
K
K
Hashizume
K
K
D000328:Adult; D000367:Age Factors; D013956:Antithyroid Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D003459:Crystallins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006111:Graves Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008713:Methimazole / Q000627:therapeutic use*; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012737:Sex Factors; D013960:Thyroid Function Tests; D013963:Thyroid Hormones / Q000097:blood; D000090803:mu-Crystallins
D013956:Antithyroid Agents; D003459:Crystallins; D012333:RNA, Messenger; D013963:Thyroid Hormones; D008713:Methimazole; D000090803:mu-Crystallins