DEVELOPMENT OF CANCER CACHEXIA-LIKE SYNDROME AND ADRENAL-TUMORS IN INHIBIN-DEFICIENT MICE
DEVELOPMENT OF CANCER CACHEXIA-LIKE SYNDROME AND ADRENAL-TUMORS IN INHIBIN-DEFICIENT MICE
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DOI：
10.1073/pnas.91.19.8817
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发表时间：
1994-09-13
影响因子：
11.1
通讯作者：
BRADLEY, A
中科院分区：
文献类型：
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作者：
MATZUK, MM;FINEGOLD, MJ;BRADLEY, A
激活素和抑制素是β-转化生长因子超家族生长调节蛋白的成员，广泛存在于多种组织中，影响多种生理过程。利用胚胎干细胞技术，我们先前证明了抑制素可以作为性腺肿瘤抑制因子发挥作用。在这项研究中，我们发现性腺肿瘤的发展迅速伴随着癌症恶病质样消瘦综合征。恶病质抑制素缺陷小鼠出现中央静脉周围的肝细胞坏死，腺胃中的壁细胞枯竭和粘膜萎缩，贫血，并表现出严重的体重减轻。肝脏病理与研究表明激活素升高对大鼠肝细胞的影响是一致的。在抑制素缺陷的肿瘤小鼠中，激活素在血清中升高10倍，可能导致一些恶病质症状。相比之下，在早期切除性腺的抑制素缺乏的小鼠不会患上这种消瘦综合征。然而，这些性腺切除、抑制素缺乏的小鼠最终发展为肾上腺皮质性类固醇激素生成肿瘤，外显率接近100%，这表明抑制素也是肾上腺的肿瘤抑制因子。
Activins and inhibins, members of the type beta transforming growth factor superfamily of growth regulatory proteins, are produced in multiple tissues and affect diverse physiologic processes. Using embryonic stem cell technology, we previously demonstrated that inhibin can function as a gonadal tumor suppressor. In this study, we show that development of gonadal tumors is rapidly followed by a cancer cachexia-like wasting syndrome. Cachectic inhibin-deficient mice develop hepatocellular necrosis around the central vein and parietal cell depletion and mucosal atrophy in the glandular stomach, are anemic, and demonstrate severe weight loss. The liver pathology is consistent with studies demonstrating an effect of elevated activins on rat hepatocytes. In inhibin-deficient mice with tumors, activins are > 10-fold elevated in the serum and are likely causing some of the cachexia symptoms. In contrast, inhibin-deficient mice gonadectomized at an early age do not develop this wasting syndrome. However, these gonadectomized, inhibin deficient mice eventually develop adrenal cortical sex steroidogenic tumors with nearly 100% penetrance, demonstrating that inhibin is also a tumor suppresser for the adrenal gland.