Effects of growth hormone on thyroid function are mediated by type 2 iodothyronine deiodinase in humans
Effects of growth hormone on thyroid function are mediated by type 2 iodothyronine deiodinase in humans
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DOI：
10.1007/s12020-017-1495-y
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发表时间：
2018-02-01
期刊：
影响因子：
3.7
通讯作者：
Inagaki, Nobuya
中科院分区：
文献类型：
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作者：
Yamauchi, Ichiro;Sakane, Yoriko;Inagaki, Nobuya
成人生长激素（GH）治疗会改变甲状腺功能，肢端肥大症通常涉及甲状腺疾病。为探讨生长激素（GH）对甲状腺功能的调节作用及其机制，我们对20例接受重组人生长激素（rhGH）治疗的严重成人GH缺乏症患者和25例接受经蝶窦手术（TSS）的肢端肥大症患者进行了回顾性研究。在这两项研究中，血清游离三碘甲状腺原氨酸（fT 3），游离甲状腺素（fT 4），和fT 3/fT 4比值进行了检查之前和之后的干预措施。我们随后给予生长激素的四个人类细胞系（HepG 2、TSA 201、MCF 7和HTC/C3），并检测碘甲腺原氨酸脱碘酶mRNA水平的变化（D1、D2和D3）。rhGH治疗后，中位血清fT 3水平从2.38 pg/mL显著增加至2.78 pg/mL（p < 0.001），fT 4从1.115降至1.065 ng/dL（p = 0.081）。TSS使中位血清fT 3从3.03 pg/mL显著降低至2.53 pg/mL（p < 0.001），并使fT 4从1.230 ng/dL增加至1.370 ng/dL（p < 0.001）。在体外实验中，GH能显著增加HTC/C3细胞D2 mRNA水平的表达（p < 0.01），并能显著增加D2蛋白及其活性，增加人血清fT 3水平，降低血清fT 4水平。我们的研究结果表明，其机制涉及D2上调。考虑到生长激素对甲状腺激素代谢的影响，甲状腺功能的数据可能有助于生长激素缺乏症和肢端肥大症的管理。
Growth hormone (GH) therapy in adults alters thyroid function, and acromegaly often involves thyroid disease. The present study aimed to elucidate roles and mechanisms of GH in regulating thyroid function.We performed two retrospective observational studies, which focused on consecutive patients with severe adult GH deficiency who received recombinant human GH (rhGH) therapy (n = 20) and consecutive patients with acromegaly who underwent transsphenoidal surgery (TSS) (n = 25). In both studies, serum free triiodothyronine (fT3), free thyroxine (fT4), and fT3/fT4 ratio were examined before and after the interventions. We subsequently administered GH to four human cell lines (HepG2, TSA201, MCF7, and HTC/C3) in vitro, and examined changes in mRNA levels of iodothyronine deiodinases (D1, D2, and D3).Median serum fT3 level significantly increased after rhGH therapy from 2.38 to 2.78 pg/mL (p < 0.001), and fT4 decreased from 1.115 to 1.065 ng/dL (p = 0.081). TSS significantly decreased median serum fT3 from 3.03 to 2.53 pg/mL (p < 0.001), and increased fT4 from 1.230 to 1.370 ng/dL (p < 0.001). In vitro, GH significantly increased D2 expression at the mRNA level in HTC/C3 cells (p < 0.01), as well as D2 protein and its activity.GH increased serum fT3 level and decreased serum fT4 level in humans. Our results suggest that its mechanism involves D2 upregulation. Considering this GH effect on thyroid hormone metabolism, data on thyroid function could be useful in the management of GH deficiency and acromegaly.