蛋白激酶C对生长激素释放激素调节人垂体腺瘤激素分泌作用的影响

Influence of protein kinase C on growth hormone releasing hormone for the regulation of human pituitary adenomas secretion

目的旨在探讨蛋白激酶C调节剂对原代培养人垂体腺瘤细胞分泌生长激素和催乳素作用的影响。方法经原代培养的人垂体腺瘤细胞与佛波醇酯共同培养,通过放射免疫学方法检测生长激素和催乳素水平,评价佛波醇酯对生长激素释放激素调节垂体腺瘤激素分泌作用的影响;同时应用DNA序列分析确定gsp癌基因突变率。结果gsp癌基因鉴定显示,18例垂体腺瘤组织标本中6例gsp癌基因表达阳性,5例突变位于201密码子,1例位于207密码子。佛波醇酯强烈刺激生长激素和催乳素的分泌并增强生长激素释放激素的刺激分泌作用,最大效应浓度为100nmol/L,使生长激素分泌水平增加2～30倍;Staurosporine作用则相反,大多数肿瘤细胞表现为明显的抑制效应,而且与gsp癌基因不相关;联合应用生长激素释放激素和佛波醇酯后使刺激分泌的作用增强,但与gsp癌基因亦无关。结论蛋白激酶C可能参与垂体腺瘤激素分泌的调控。

Objective To investigate the influence of protein kinase C （PKC） regulator on the growth hormone （GH） and prolactin （PRL） secretion in primary cultured cells of human pituitary adenomas. Methods Primarily cultured cells of human pituitary adenomas were co-cultured with phorbol ester. GH and PRL levels were examined by radioimmunoassay to evaluate the effect of phorbol ester on the regulation of hormone secretion in pituitary adenomas by GH releasing hormone （GHRH）. Mutation rate of gsp oncogene was identified by DNA sequential analysis. Results Among 18 tissue amples of pituitary adenomas, 6 samples showed gsp oncogene positive, and mutational sites were detected at codon 201 in 5 samples and codon 207 in 1 sample. Phorbol ester strongly stimulated GH and PRL secretion and enhanced the GHRH stimulating effect. The maximum effective concentration was 100 nmol/L which may increase GH secretion level 2-30 folds. In contrast, staurosporine exerted a significant inhibitory effect in most tumor cells. The effects were not related to gsp oncogene. Combination of GHRH and phorbol ester can strongly stimulate the secretion, but was also unrelated to gsp oncogene. Conclusion PKC may involve in the regulation of hormone secretion in pituitary adenomas.