Stefaneanu L, Kovacs K, Horvath E, Buchfelder M, Fahlbusch R, Lancranjan L
Department of Laboratory Medicine, St. Michael's Hospital, University of Toronto, Ontario, Canada.
Endocrine. 2001 Apr;14(3):329-36. doi: 10.1385/endo:14:3:329.
The inhibitory effects of dopamine on adenohypophysial cells are mediated via dopamine subtype 2 receptor (D2R). Dopamine agonists inhibit hormone release and induce tumor shrinkage in most prolactin-secreting adenomas, whereas in other adenoma types such effects are sporadic. We investigated D2R gene expression by in situ hybridization (ISH) and immunocytochemistry in different types of pituitary adenomas. By ISH, a variable D2R signal was detected in 79 of 89 cases: 4 of 6 densely granulated and 8 of 8 sparsely granulated somatotroph, 4 of 4 mammosomatotroph, 7 of 7 mixed somatotroph-lactotroph, 4 of 4 acidophil stem cell, 16 of 16 sparsely granulated lactotroph, 11 of 16 corticotroph (functioning and silent), 3 of 4 silent subtype 3, 5 of 5 thyrotroph, 5 of 6 gonadotroph, 5 of 6 null cell, and 7 of 7 oncocytic adenomas. By immunocytochemistry, D2R protein was localized in cytoplasm and nuclei of 60 of 62 adenomas. In lactotroph adenomas, long-acting bromocriptine (BEC-LAR) induced a major increase in D2R mRNA, which was not accompanied by increased D2R immunoreactivity, suggesting mRNA stabilization. In conclusion, D2R gene is expressed in the majority of pituitary adenomas representing all tumor types. The significance of nuclear localization of D2R protein remains to be clarified.
多巴胺对腺垂体细胞的抑制作用是通过多巴胺2型受体(D2R)介导的。多巴胺激动剂可抑制大多数催乳素分泌性腺瘤的激素释放并诱导肿瘤缩小,而在其他类型的腺瘤中,这种作用则是偶发的。我们通过原位杂交(ISH)和免疫细胞化学方法研究了不同类型垂体腺瘤中D2R基因的表达。通过ISH,在89例中的79例检测到可变的D2R信号:6例密集颗粒型生长激素细胞腺瘤中的4例、8例稀疏颗粒型生长激素细胞腺瘤中的8例、4例乳腺生长激素细胞腺瘤中的4例、7例生长激素-催乳素混合细胞腺瘤中的7例、4例嗜酸性干细胞腺瘤中的4例、16例稀疏颗粒型催乳素细胞腺瘤中的16例、16例促肾上腺皮质激素细胞腺瘤(功能性和静止性)中的11例、4例静止性3型腺瘤中的3例、5例促甲状腺激素细胞腺瘤中的5例、6例促性腺激素细胞腺瘤中的5例、6例无功能细胞腺瘤中的5例以及7例嗜酸性细胞瘤中的7例。通过免疫细胞化学,D2R蛋白定位于62例腺瘤中60例的细胞质和细胞核中。在催乳素细胞腺瘤中,长效溴隐亭(BEC-LAR)可诱导D2R mRNA显著增加,但这并未伴随D2R免疫反应性的增加,提示mRNA稳定。总之,D2R基因在代表所有肿瘤类型的大多数垂体腺瘤中均有表达。D2R蛋白核定位的意义仍有待阐明。