Sergi I, Medri G, Papandreou M J, Gunz G, Jaquet P, Ronin C
Laboratoire d'Immunochimie des Hormones Glycoprotéiques, Marseille, France.
J Endocrinol Invest. 1993 Jan;16(1):45-55. doi: 10.1007/BF03345829.
To understand better why patients with TSH-secreting pituitary tumors exhibit variable degree of hyperthyroidism, we analyzed the various isoforms of TSH and alpha-subunit secreted by 4 TSH-secreting adenomas in primary culture. All patients had macrodenomas clinically associated with hyperthyroidism with normal to elevated TSH plasma levels. The in vivo molar alpha/TSH ratio ranged from 18.4 to 3.8. The hormone material secreted over 4 to 48 h in culture was separated by gel isoelectrofocusing, eluted and estimated by immunoassays. The release of free alpha-subunit was noticeably different among adenomas. Three tumors were found to release an homogeneous and acidic (pI = 5.4-4.5) species totally unrelated to the alpha-subunit dissociated from intrapituitary TSH (5 isoforms, pI = 8.8-5.8) while another was more heterogeneous (pI = 8.8, 8.4, 7.6, 6.8, 5.8, 5.4-4.5). Tumoral TSH exhibited at least six detectable isoforms (pI = 8.6, 8.3-8.0, 7.5, 7.0, 6.5, 6.0) very similar to those present in a purified intrapituitary hormone preparation. While intrapituitary TSH was composed of 70% of alkaline (pI = 8.6-7.5), 25% of neutral (pI = 7.0-6.0) and 5% (pI = 5.8-4.5) of acidic forms, these species were found to be more evenly distributed in adenomatous secretion (43%/42%/15%). The TSH-secreting tumors thus appeared to relase preferentially neutral and acidic forms of TSH than alkaline components but for one tumor, this ratio could be modified by chronic incubation with TRH. When assayed for their capacity to stimulate 3H-thymidine incorporation in FRTL-5 cells, neutral TSH appeared definitely less potent than the alkaline and acidic isohormones. Altogether, these data show that pituitary adenomas synthesize normal forms of TSH but release them in variable amount in the medium. When circulating in the blood, the ratio between active and inactive isoforms of TSH may thus be responsible for the variable stimulation of the thyroid gland observed in the patients.
为了更好地理解促甲状腺激素（TSH）分泌型垂体瘤患者为何表现出不同程度的甲状腺功能亢进，我们分析了原代培养的4例TSH分泌性腺瘤所分泌的TSH和α亚基的各种同工型。所有患者均有与甲状腺功能亢进相关的大腺瘤，血浆TSH水平正常或升高。体内α/TSH摩尔比在18.4至3.8之间。通过凝胶等电聚焦分离培养4至48小时所分泌的激素物质，洗脱后通过免疫测定进行评估。腺瘤之间游离α亚基的释放明显不同。发现3个肿瘤释放出一种均一的酸性（pI = 5.4 - 4.5）物质，与从垂体TSH解离的α亚基完全无关（5种同工型，pI = 8.8 - 5.8），而另一个则更为不均一（pI = 8.8、8.4、7.6、6.8、5.8、5.4 - 4.5）。肿瘤性TSH表现出至少6种可检测到的同工型（pI = 8.6、8.3 - 8.0、7.5、7.0、6.5、6.0），与纯化的垂体激素制剂中存在的同工型非常相似。虽然垂体TSH由70%的碱性（pI = 8.6 - 7.5）、25%的中性（pI = 7.0 - 6.0）和5%（pI = 5.8 - 4.5）的酸性形式组成，但发现这些形式在腺瘤分泌中分布更为均匀（43%/42%/15%）。因此，TSH分泌型肿瘤似乎优先释放中性和酸性形式的TSH而非碱性成分，但对于一个肿瘤，这种比例可通过与促甲状腺激素释放激素（TRH）长期孵育而改变。当检测它们刺激FRTL - 5细胞中3H - 胸腺嘧啶掺入的能力时，中性TSH的效力明显低于碱性和酸性同工激素。总之，这些数据表明垂体腺瘤合成正常形式的TSH，但在培养基中释放的量不同。当在血液中循环时，TSH活性和非活性同工型之间的比例可能因此导致患者中观察到的甲状腺不同程度的刺激。
