Osamura R Y, Oda K, Utsunomiya H, Inada K, Umemura S, Shibuya M, Katakami H, Voss J W, Mayo K E, Rosenfeld M G
Department of Pathology, Tokai University School of Medicine, Kanagawa, Japan.
Endocr J. 1993 Feb;40(1):133-9. doi: 10.1507/endocrj.40.133.
It has been suggested that pit-1 protein may play a role in the differentiation of the anterior pituitary cells. The present immunohistochemical studies were designed to elucidate the relationship between functional differentiation of pituitary adenoma and expression of pit-1 protein in human (h) GRF transgenic mice. Pituitaries from a 10 month old and a 6 month old transgenic mice were fixed in 4% paraformaldehyde and embedded in paraffin. The indirect immunoperoxidase method was performed using antibodies against hGRF, GH, PRL, ACTH, alpha subunit (SU), FSH beta SU, LH beta SU, TSH beta SU, and pit-1 protein. Immunohistochemical double staining was performed at light and electron microscopic levels. The pituitary glands of hGRF transgenic mice (both 10 month and 6 month old) demonstrated diffuse hyperplasia of GH positive cells with coexpression of hGRF within the same cells. There were also scattered cells which were positive for other hormones and hormone subunits in the hyperplastic pituitary. Three discrete nodules were found in the pituitary gland of a 10 month old hGRF transgenic mouse and were identified as adenomas. These adenomas were composed of enlarged round cells which were positive only for GH, hGRF, PRL and TSH beta SU. Pit-1 protein was intensely expressed in the nuclei of the adenoma cells. These results suggest the existence of an autocrine mechanism by hGRF in the formation of somato-lacto-thyrotroph adenoma via constitutive pit-1 expression.
有人提出，Pit-1蛋白可能在前脑垂体细胞的分化中发挥作用。本免疫组织化学研究旨在阐明人（h）GRF转基因小鼠垂体腺瘤的功能分化与Pit-1蛋白表达之间的关系。将10月龄和6月龄转基因小鼠的垂体用4%多聚甲醛固定，石蜡包埋。采用抗hGRF、GH、PRL、ACTH、α亚基（SU）、FSHβ亚基、LHβ亚基、TSHβ亚基和Pit-1蛋白的抗体进行间接免疫过氧化物酶法检测。在光镜和电镜水平进行免疫组织化学双重染色。hGRF转基因小鼠（10月龄和6月龄）的垂体显示GH阳性细胞弥漫性增生，且同一细胞内共表达hGRF。增生的垂体中也有散在的其他激素和激素亚基阳性的细胞。在一只10月龄hGRF转基因小鼠的垂体中发现了三个离散的结节，被鉴定为腺瘤。这些腺瘤由仅对GH、hGRF、PRL和TSHβ亚基呈阳性的圆形增大细胞组成。Pit-1蛋白在腺瘤细胞核中强烈表达。这些结果表明，hGRF通过组成性Pit-1表达在生长激素-催乳素-促甲状腺素腺瘤形成中存在自分泌机制。
