Somatotroph to thyrotroph cell transdifferentiation during experimental hypothyroidism ‐ a light and electron‐microscopy study
Somatotroph to thyrotroph cell transdifferentiation during experimental hypothyroidism ‐ a light and electron‐microscopy study
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实验性甲状腺功能减退期间生长激素细胞向促甲状腺细胞的转分化——光学和电子显微镜研究
DOI：
10.1111/j.1582-4934.2003.tb00230.x
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发表时间：
2003
影响因子：
5.3
通讯作者：
J. Morris
中科院分区：
文献类型：
--
作者：
Ş. Radian;M. Coculescu;J. Morris
垂体生长营养细胞和甲状腺营养细胞在个体发育过程中有共同的前体细胞表达转录因子Pitl。在成年大鼠垂体和肢端肥大症患者的垂体腺瘤中发现了同时表达促甲状腺素（TSH）和生长激素（GH）的细胞，这些肿瘤同时含有促甲状腺素释放激素（TRH）和促甲状腺素受体（TRHR）。研究表明，刺激原发性甲状腺功能减退患者的TSH表达可促进促生长细胞向促甲状腺细胞转分化的变化。我们验证了这一假设和TRH在实验性原发性甲状腺功能减退大鼠中的作用。6个月大的成年雌性Long - Evans大鼠在饮用水中给予抗甲状腺药物甲巯咪唑（0.1% w/v） 42天。动物在麻醉下每隔一周进行灌注固定，并在丙烯酸树脂中处理垂体组织进行免疫荧光和免疫电镜检测TSH、GH和TRHR。甲巯咪唑给药后，甲状腺功能减退大鼠垂体免疫荧光生长因子数量显著减少，逐渐被促甲状腺因子所取代。我们注意到生长激素和TSH在同一细胞中的共定位。免疫电镜显示甲状腺肥大，粗糙的内质网扩张，含有电子致密物质和内质网颗粒，两者对TSH（“甲状腺切除细胞”）都有免疫反应。生长激素表现出生长激素免疫反应性降低，并且存在TSH型小尺寸分泌颗粒。这表明，甲巯咪唑诱导的甲状腺功能减退症中TSH细胞数量的显著增加，至少部分是由于生长营养细胞向甲状腺营养细胞的转分化。TRHR免疫荧光在正常大鼠垂体的许多生长因子中表达，与免疫反应性GH不同，其表达在甲状腺功能减退时增强。TRHR -免疫反应细胞的数量与TSH -免疫反应细胞的数量平行增加。这表明TRH刺激在转分化过程中起作用。综上所述，这些数据表明，除了涉及早期全潜能祖细胞的细胞突变机制外，现有生长营养细胞的转分化也在多激素GH分泌腺瘤的发病机制中起作用。
Somatotroph and thyrotroph pituitary cells share a common precursor cell expressing the transcription factor Pitl in ontogeny. Cells expressing both thyrotropin (TSH) and growth‐hormone (GH) are found in adult rat pituitary and in human pituitary adenomas in acromegaly, and these tumors contain both thyrotropin‐releasing hormone (TRH) and the TRH receptors (TRHR). It has been shown that stimulation of TSH expression in primary hypothyroidism promotes changes suggestive of somatotroph to thyrotroph cell transdifferentiation. We tested this hypothesis and the role of TRH in experimental primary hypothyroidism in rats. Adult female Long‐Evans rats, 6 months old, were administered the antithyroid drug methimazole (0,1% w/v) in the drinking water for 42 days. Animals were sacrificed by perfusion fixation under anaesthesia at weekly intervals and pituitary tissue processed in acrylic resin for immunofluorescence and immuno‐electronmicroscopy for TSH, GH and TRHR. In the hypothyroid rat pituitary immunofluorescent somatotrophs were greatly reduced in number and gradually replaced by thyrotrophs during methimazole administration. Colocalization of GH and TSH in the same cell was noted. Immunoelectronmicroscopy demonstrated the development of enlarged thyrotrophs with dilated rough endoplasmic reticulum containing an electron‐dense material and intracisternal granules, both of which are immunoreactive for TSH (‘thyroidectomy cells’). The somatotrophs showed reduced GH immunoreactivity and also the presence of TSH‐type, small‐size secretory granules. This suggests that, the greatly increased number of TSH‐cells in methimazole‐induced‐hypothyroidism is due, at least partially, to the transdifferentiation of somatotroph into thyrotroph cells. TRHR immunofluorescence was expressed in many somatotrophs in normal rat pituitary and unlike immunoreactive GH, its expression was enhanced during hypothyroidism. The number of TRHR‐immunoreactive cells increased in parallel with the number of TSH‐immunoreactive cells. This indicates a role for TRH stimulation in the transdifferentiation process. Taken together, these data suggest that, in addition to the cell mutation mechanism involving an early totipotential progenitor cell, transdifferentiation of existing somatotroph cells also plays a part in the pathogenesis of multihormonal GH‐secreting adenomas.
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类固醇可以调节牛垂体培养物中催乳素和生长激素细胞的转分化。
影响因子：
4.8
作者：
Kineman,RD;Faught,WJ;Frawley,LS
通讯作者：
Frawley,LS
垂体前叶中促甲状腺素释放激素（TRH）基因的表达。
影响因子：
4.8
作者：
Bruhn,TO;Rondeel,JM;Bolduc,TG;Jackson,IM
通讯作者：
Jackson,IM
影响因子：
10.5
作者：
BEHRINGER, RR;MATHEWS, LS;BRINSTER, RL
通讯作者：
BRINSTER, RL
分泌 GH 和 TSH 的垂体腺瘤对生长抑素类似物的反应 (SMS 201-995)：证据表明 GH 和 TSH 共存于同一细胞和分泌颗粒中。
影响因子：
4.1
作者：
Malarkey,WB;Kovacs,K;O'Dorisio,TM
通讯作者：
O'Dorisio,TM
丙基硫氧嘧啶诱导的甲状腺功能减退症导致生长激素可逆地转分化为甲状腺切除细胞。
DOI：
--
发表时间：
1990
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
Horvath,E;Lloyd,RV;Kovacs,K
通讯作者：
Kovacs,K