We have studied the expression of
type II iodothyronine deiodinase (DII) in human thyroid
tumors and cultured human thyroid cells to elucidate the mechanisms involved in the regulation of DII expression in human thyroid gland. Three cases with
hyperfunctioning thyroid adenoma, including a case that showed an activating mutation of
G(s)alpha with a constitutive activation of cAMP production in cultured cells, and six cases with
papillary thyroid carcinoma were analyzed in the present study. Free T(3) was increased, whereas free T(4) was within the normal range in all patients with
hyperfunctioning thyroid adenoma. Thyroid
tumor tissue and surrounding nontumor tissue were obtained at the time of surgery, and DII expression was compared between
tumor tissue and nontumor tissue in each case. Northern analysis demonstrated the presence of DII
messenger RNA (
mRNA) approximately 7.5 kb in size in all of the
tumor and nontumor tissues. DII
mRNA and DII activity in
hyperfunctioning thyroid adenoma were significantly increased compared with those in nontumor tissue in each case. In contrast, DII
mRNA and DII activity in
papillary thyroid carcinoma were decreased compared with those in nontumor tissue in each case. DII
mRNA and DII activity in cultured human thyroid cells were significantly stimulated by TSH in a dose-dependent manner. The promoter activity of the human DII gene including the complete cAMP response element, transfected to cultured human thyroid cells, was stimulated by (Bu)(2)cAMP. In summary, these results suggest that DII expression in human thyroid gland is regulated at the transcriptional level through the
TSH receptor-
G(s)alpha-cAMP regulatory cascade, which may be related to the increase in circulating T(3) level in patients with
Graves' disease and
hyperfunctioning thyroid adenoma.