Glial-derived neurotropic factor and RET gene expression in normal human anterior pituitary cell types and in pituitary tumors
Glial-derived neurotropic factor and RET gene expression in normal human anterior pituitary cell types and in pituitary tumors
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DOI：
10.1210/jc.87.4.1879
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发表时间：
2002-04-01
影响因子：
5.8
通讯作者：
Alvarez, CV
中科院分区：
文献类型：
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作者：
Japón, MA;Urbano, AG;Alvarez, CV
胶质源性神经营养因子(GDNF)信号转导途径是由GDNT受体-α(GFRcalpha1)组成的两组分系统介导的。该复合体激活酪氨酸激酶受体RET。在这篇文章中，我们证明了GDNF、GFRalpha1和RET的mRNA和蛋白在人的垂体前叶中的表达。垂体前叶切片双重免疫组织化学染色显示，95%以上的促生长激素细胞呈GDNF免疫反应，皮质促性腺激素细胞表达较少(20%)，其余细胞几乎不表达GDNF。此外，虽然95%以上的生长激素细胞被RET染色，但在其他类型的细胞中没有检测到阳性免疫染色。此外，我们还在不同激素表型的人垂体腺瘤中寻找GDNF和RET。C-RET在所有筛查的GH分泌性腺瘤以及50%的ACTH腺瘤中均呈强阳性表达。GDNF在所有GH腺瘤和10%的促肾上腺皮质激素瘤中均呈阳性表达。最后，我们发现GFRalpha1在90%的生长激素瘤和50%的促肾上腺皮质激素瘤以及1/8的催乳素瘤和1/13的无功能腺瘤中呈强阳性表达。所有剩余的垂体瘤RET、GDNF和GFRAlpha1均为阴性。本研究表明GDNF可能在调节正常人垂体前叶的促生长激素细胞生长和/或细胞功能方面起作用。RET在所有生长激素瘤和50%产生ACTH的肿瘤中均有表达，提示GDNF和RET可能参与了垂体瘤的发生。
Glial-derived neurotropic factor (GDNF) signaling is mediated through a 2-component system consisting of the so-called GDNF receptor-alpha (GFRcalpha1), which binds to GDNT. This complex activates the tyrosine kinase receptor RET. In this paper we demonstrate GDNF, GFRalpha1, and RET mRNA and protein expression in the human anterior pituitary gland. Double immunohistochemistry of anterior pituitary sections showed GDNF immunoreactivity in more than 95% of somatotrophs and to a lesser extent in corticotrophs (20%); it was almost absent in the remaining cell types. Also, although more than 95% of somatotrophs were stained for RET, no positive immunostaining could be detected in other cell types. Furthermore, we have looked for GDNF and RET in human pituitary adenomas of various hormonal phenotypes. Strong positive immunostaining was found for c-RET in all of the GH-secreting adenomas screened as well as in 50% of ACTH-producing adenomas. Positive immunostaining for GDNF was found in all of the GH-secreting adenomas and in 10% of the corticotropinomas. Lastly, we found strong positive immunostaining for GFRalpha1 in 90% of the somatotropinomas and 50% of the corticotropinomas as well as in 1 of 8 prolactinomas and 1 of 13 nonfunctioning adenomas. All of the remaining pituitary tumors screened were negative for RET, GDNF, and GFRalpha1.This study indicates that GDNF may well be acting in the regulation of somatotroph cell growth and/or cell function in the normal human anterior pituitary gland. The expression of RET in all of the somatotropinomas and in 50% of the ACTH-producing tumors implies that GDNF and RET could be involved in the pathogenesis of pituitary tumors.