Giacomini Damiana, Acuña Matías, Gerez Juan, Nagashima Alberto Carbia, Silberstein Susana, Páez-Pereda Marcelo, Labeur Marta, Theodoropoulou Marily, Renner Ulrich, Stalla Günter K, Arzt Eduardo
Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología y Biología Molecular y Celular, FCEN, Universidad de Buenos Aires, Buenos Aires, Argentina.
Neuroendocrinology. 2007;85(2):94-100. doi: 10.1159/000100428. Epub 2007 Feb 28.
The anterior pituitary can develop benign tumors of different sizes, classified as micro- and macroadenomas, frequently associated with high levels of hormone production, leading to different associated syndromes like Cushing's disease, acromegaly or prolactinomas. Much work has been done in order to understand the signaling pathways and the factors and hormones involved in the pituitary tumorigenic process. In recent years, much evidence has been collected and it is now well documented that cytokines of the gp130 family, such as interleukin-6, that use gp130 as a common signaling protein stimulate not only the proliferation but also the hormone secretion of pituitary cells. Experiments in vivo have shown that the overexpression of the gp130 receptor resulted in pituitary abnormal growth. Moreover, it has been recently described that bone morphogenetic protein-4 (BMP-4), a member of the TGF-beta family, has a stimulatory role on lactosomatotropic cells promoting the development of prolactinomas but it has an inhibitory action on the corticotropic lineage. This inhibitory action prevents Cushing's disease progression. Furthermore, BMP-4 mediates the antiproliferative action of retinoic acid in these cells. The present review highlights the most recent work about gp130 and TGF-beta cytokine families and their role in pituitary tumorigenesis.
垂体前叶可发生不同大小的良性肿瘤，分为微腺瘤和大腺瘤，常与高水平的激素分泌有关，可导致不同的相关综合征，如库欣病、肢端肥大症或催乳素瘤。为了了解垂体肿瘤发生过程中涉及的信号通路以及相关因子和激素，人们已经开展了大量工作。近年来，已收集到许多证据，现在有充分的文献记载表明，gp130家族的细胞因子，如白细胞介素-6，它们以gp130作为共同的信号蛋白，不仅刺激垂体细胞的增殖，还刺激其激素分泌。体内实验表明，gp130受体的过表达会导致垂体异常生长。此外，最近有研究表明，转化生长因子-β家族成员骨形态发生蛋白-4（BMP-4）对催乳生长激素细胞具有刺激作用，可促进催乳素瘤的发展，但对促肾上腺皮质激素细胞系具有抑制作用。这种抑制作用可阻止库欣病的进展。此外，BMP-4介导视黄酸在这些细胞中的抗增殖作用。本综述重点介绍了关于gp130和转化生长因子-β细胞因子家族及其在垂体肿瘤发生中作用的最新研究成果。
