Giorgi R R, Chile T, Bello A R, Reyes R, Fortes M A H Z, Machado M C, Cescato V A, Musolino N R, Bronstein M D, Giannella-Neto D, Corrêa-Giannella M L
Laboratory for Cellular and Molecular Endocrinology (LIM-25), University of São Paulo School of Medicine, São Paulo, Brazil.
J Neuroendocrinol. 2008 Sep;20(9):1052-7. doi: 10.1111/j.1365-2826.2008.01761.x. Epub 2008 Jul 8.
The neurotensin (NT) produced in the hypothalamus and in pituitary gonadotrophs and thyrotrophs participates in neuroendocrine regulation. Recently, the involvement of this peptide in normal and neoplastic cell proliferation has been postulated. In the present study, we evaluated the expression of NT and its receptors (NTR1, 2 and 3) in a series of 50 pituitary adenomas [11 growth hormone (GH)-, eight prolactin (PRL)-, four adrenocorticotrophic hormone (ACTH)- and 27 nonfunctioning adenomas]. NT mRNA expression was significantly higher in functioning compared to nonfunctioning adenomas and with normal pituitary. Nonfunctioning pituitary adenomas showed lower expression of NT mRNA than normal pituitary. In the immunohistochemical study of functioning adenomas, NT was colocalised with GH, PRL and ACTH secreting cells. In nonfunctioning adenomas, the NT immunoreactivity intensity was variable among the samples. NTR3 mRNA expression was observed in all examined samples and was higher in the adenomas, both functioning and nonfunctioning, compared to normal pituitary. By contrast, NTR1 and NTR2 mRNA were not detected in either pituitary adenomas or normal tissue. The higher expression of NTR3, as well as the expression of NT by tumoural corticotrophs, lactotrophs and somatotrophs, which are cells types that do not express this peptide in the normal pituitary, suggests that NT autocrine and/or paracrine stimulation mediated by NTR3 may be a mechanism associated with the tumourigenesis of functioning adenomas.
在下丘脑以及垂体促性腺细胞和促甲状腺细胞中产生的神经降压素（NT）参与神经内分泌调节。最近，有人推测这种肽参与正常和肿瘤细胞的增殖。在本研究中，我们评估了50例垂体腺瘤（11例生长激素（GH）腺瘤、8例催乳素（PRL）腺瘤、4例促肾上腺皮质激素（ACTH）腺瘤和27例无功能腺瘤）中NT及其受体（NTR1、2和3）的表达。与无功能腺瘤和正常垂体相比，功能性腺瘤中NT mRNA表达显著更高。无功能垂体腺瘤中NT mRNA表达低于正常垂体。在对功能性腺瘤的免疫组织化学研究中，NT与分泌GH、PRL和ACTH的细胞共定位。在无功能腺瘤中，不同样本间NT免疫反应强度存在差异。在所有检测样本中均观察到NTR3 mRNA表达，与正常垂体相比，功能性和无功能腺瘤中的表达均更高。相比之下，在垂体腺瘤或正常组织中均未检测到NTR1和NTR2 mRNA。NTR3的较高表达，以及肿瘤促肾上腺皮质激素细胞、催乳激素细胞和生长激素细胞中NT的表达，而这些细胞类型在正常垂体中不表达这种肽，提示由NTR3介导的NT自分泌和/或旁分泌刺激可能是与功能性腺瘤肿瘤发生相关的一种机制。
