STUDIES OF TWO THYROTROPHIN‐SECRETING PITUITARY ADENOMAS: EVIDENCE FOR DOPAMINE RECEPTOR DEFICIENCY
STUDIES OF TWO THYROTROPHIN‐SECRETING PITUITARY ADENOMAS: EVIDENCE FOR DOPAMINE RECEPTOR DEFICIENCY
复制标题
对两种分泌甲状腺激素的垂体腺瘤的研究：多巴胺受体缺陷的证据
作者：
J. Bevan;C. Burke;M. Esiri;C. Adams;M. Ballabio;M. Nissim;G. Faglia
在先前报道的22例使用多巴胺激动剂治疗的TSH分泌垂体腺瘤患者中，18例血清TSH没有下降。这些罕见肿瘤的体外研究很少，因此多巴胺能耐药的机制仍然不清楚。我们描述了另外两例甲状腺腺瘤患者；第一次是甲状腺毒性（T3 6.1 nmol/l, TSH 7 mU/l），第二次是放射性碘后诊断为Graves病。第二例患者α -亚单位：TSH摩尔比小于1（0.27）。将体内TSH对TRH、溴隐亭和多潘立酮的反应与体外切除肿瘤细胞的反应进行比较，后者使用连续浸润系统进行研究。利用3H - spiperone放射受体试验在每个肿瘤的膜中寻找多巴胺受体。患者1在200 μg TRH （i.v）后血清TSH （7 ~ 13 mU/l）和α‐亚单位（18.7 ~ 385 ng/ml）显著升高，但患者2未见明显升高（TSH: 69 ~ 72 mU/l， α‐亚单位：4.9 ~ 5.2 ng/ml）。两名患者口服溴隐亭2.5 mg或多潘立酮10 mg后血清TSH均无变化，但血清PRL反应正常。患者1的血清TSH分子大小明显正常，但生物活性增加（B/I比3.8）；患者2的血清TSH分子大小增加，但生物活性降低（B/I比0.1）。每位患者的肿瘤细胞进行TSHβ和α‐亚基免疫染色，并在体外分泌TSH。第1种小鼠在TRH （1 ~ 100 ng/ml）后TSH释放呈剂量依赖性，多巴胺（5 μmol/l）不能抑制其释放，而第2种小鼠对TRH无反应。两种肿瘤均未显示多巴胺（5 μmol/l）或溴隐碱（0.01-10 nmol/l）对TSH释放的抑制作用，且均不含膜结合多巴胺受体。结果表明，大多数分泌TSH的垂体腺瘤典型的多巴胺能抵抗可能是由于膜结合多巴胺受体的改变或缺失。
Of 22 previously reported patients with TSH‐secreting pituitary adenomas challenged with dopamine agonists, 18 showed no decrease in serum TSH. There have been few in‐vitro studies of these rare tumours so the mechanism of the dopaminergic resistance has remained obscure. We describe two further patients with thyrotrophinomas; the first was thyrotoxic (T3 6.1 nmol/l, TSH 7 mU/l) and the second was diagnosed after radioiodine for presumed Graves’disease. The second patient had an α‐subunit: TSH molar ratio less than unity (0.27). In‐vivo TSH responses to TRH, bromocriptine and domperidone were compared with those of the resected tumour cells in vitro, the latter studied using a continuous perifusion system. Dopamine receptors were sought in membranes from each tumour using a radioreceptor assay employing 3H‐spiperone. Patient 1 showed significant increases in serum TSH (7 to 13 mU/l) and α‐subunit (18.7 to 385 ng/ml) after 200 μg TRH (i.v.) but patient 2 showed no such increases (TSH: 69 to 72 mU/l, α‐subunit: 4.9 to 5.2 ng/ml). Neither patient showed a change in serum TSH following bromocriptine 2.5 mg (orally) or domperidone 10 mg (i.v.), though serum PRL responded normally. Serum TSH from patient 1 was of apparently normal molecular size but increased bioactivity (B/I ratio 3.8) and that from patient 2 was of increased molecular size but reduced bioactivity (B/I ratio 0.1). Tumour cells from each patient immunostained for TSHβ and α‐subunit, and secreted TSH in vitro. The first showed dose‐dependent TSH release after TRH (1–100 ng/ml) which could not be inhibited by dopamine (5 μmol/l) but the second was unresponsive to TRH in vitro. Neither tumour showed inhibition of TSH release by dopamine (5 μmol/l) or bromocriptine (0.01–10 nmol/l) and neither contained membrane‐bound dopamine receptors. The results suggest that the dopaminergic resistance typical of most TSH‐secreting pituitary adenomas may be due to altered or absent membrane‐bound dopamine receptors.
单层培养中人促甲状腺肿瘤细胞产生 TSH 和 TSH 亚基。
DOI：
10.1530/acta.0.0990224
发表时间：
1982
期刊：
Acta endocrinologica
影响因子：
--
作者：
Filetti,S;Rapoport,B;Aron,DC;Greenspan,FC;Wilson,CB;Fraser,W
通讯作者：
Fraser,W