Jin L, Maeda T, Chandler W F, Lloyd R V
Department of Pathology, University of Michigan Medical Center, Ann Arbor 48109-0054.
Am J Pathol. 1993 Feb;142(2):569-78.
Protein kinase C (PKC) is involved in the differentiation and growth regulation of a variety of tissues including anterior pituitary gland cells. To determine the distribution of PKC in different types of adenomas, PKC activity was analyzed in human pituitary tumors and the effects of hypothalamic hormone stimulation on PKC activity were examined in cultured adenoma cells. Gonadotroph (LH/FSH) and null cell adenomas had significantly higher levels of particulate, soluble, and total PKC activity compared with growth hormone (GH) adenomas (P < 0.05). Chronic stimulation of null cell adenomas with gonadotropin hormone-releasing hormone or of one GH adenoma with GH-releasing hormone for 7 days did not significantly alter total PKC activity in pituitary cells cultured in serum-free medium. Localization of the calcium-dependent PKC isozymes (alpha, beta and gamma) by immunohistochemistry and in situ hybridization revealed predominantly PKC alpha in all adenomas and variable expression of PKC beta and gamma in some tumors. When the calcium-independent PKC isozymes (delta, epsilon, and zeta) were localized by in situ hybridization, normal and neoplastic pituitaries expressed abundant mRNA for PKC epsilon, whereas some tumors and one normal pituitary had a few cells positive for PKC zeta mRNA as evaluated by grain density and the number of cells labeled. These results indicate that there is a variable distribution of PKC mRNA isozymes in human pituitary adenomas and that normal pituitaries and pituitary adenoma cells express the mRNA for both the calcium-dependent and some of the calcium-independent PKC isozymes. Chronic treatment with the hypothalamic gonadotropin hormone-releasing hormone and GH-releasing hormone, which increased LH/FSH and GH secretion, respectively, did not increase PKC activity in cultured adenoma cells. The presence of calcium-dependent and calcium-independent PKC isozymes in normal and neoplastic pituitary cells indicates that PKC probably plays a major role in signal transduction in the human pituitary adenomas examined in this study.
蛋白激酶C（PKC）参与包括垂体前叶细胞在内的多种组织的分化和生长调节。为了确定PKC在不同类型腺瘤中的分布，对人垂体肿瘤中的PKC活性进行了分析，并在培养的腺瘤细胞中检测了下丘脑激素刺激对PKC活性的影响。与生长激素（GH）腺瘤相比，促性腺激素（LH/FSH）腺瘤和无功能细胞腺瘤的颗粒性、可溶性和总PKC活性水平显著更高（P < 0.05）。用促性腺激素释放激素长期刺激无功能细胞腺瘤或用生长激素释放激素长期刺激一个GH腺瘤7天，并未显著改变在无血清培养基中培养的垂体细胞的总PKC活性。通过免疫组织化学和原位杂交对钙依赖性PKC同工酶（α、β和γ）进行定位，结果显示所有腺瘤中主要为PKCα，在一些肿瘤中PKCβ和γ的表达存在差异。当通过原位杂交对非钙依赖性PKC同工酶（δ、ε和ζ）进行定位时，正常垂体和肿瘤性垂体均表达丰富的PKCε mRNA，而根据颗粒密度和标记细胞数量评估，一些肿瘤和一个正常垂体中有少数细胞PKCζ mRNA呈阳性。这些结果表明，人垂体腺瘤中PKC mRNA同工酶的分布存在差异，正常垂体和垂体腺瘤细胞表达钙依赖性和部分非钙依赖性PKC同工酶的mRNA。分别增加LH/FSH和GH分泌的下丘脑促性腺激素释放激素和生长激素释放激素的长期治疗，并未增加培养的腺瘤细胞中的PKC活性。正常和肿瘤性垂体细胞中存在钙依赖性和非钙依赖性PKC同工酶，表明PKC可能在本研究中检测的人垂体腺瘤的信号转导中起主要作用。
