多种细胞内第二信使在人垂体生长激素腺瘤生长激素分泌的调控作用

The regulation of multiple intracellular "second messengers" on growth hormone secretion by human pituitary somatotrophinomas

目的 探讨多种第二信使在人垂体生长激素 (GH)腺瘤GH分泌的调控作用。方法采用 1 8例体外人垂体GH腺瘤细胞培养方法观察第二信使cAMP、三磷酸肌醇 (IP3)和Ca2 +在GH释放中的调节效应 ,肿瘤组织同时采用聚合酶链式反应和直接序列分析法评价 gsp癌基因的表达。结果 6/1 8(3 3 % )为 gsp癌基因阳性 ,其中 1 1例肿瘤观察了人工合成GH释放剂 (GHRP 6)和GH释放激素 (GHRH)对cAMP水平的相互影响 ,GHRP 6在 9例 gsp阴性对cAMP产生差异无显著性(P >0 .0 5) ,而在 2例 gsp阳性组中却表现出有显著性的cAMP产生刺激效应。且GHRP 6可增加 gsp癌基因阴性组GHRH所致cAMP产生效应。钙调蛋白抑制剂W 7和蛋白激酶C抑制剂均可减低GHRP 6所致的GH分泌。结论 在GH的分泌调节过程中有多种第二信使的介入。

Objective To investigate the regulatory effects of multiple intracellular 'second messengers' on growth hormone (GH) secretion by human pituitary somatotrophinomas.Methods Using cell culture in vitro and PCR direct sequencing,the regulatory effects of intracellular second messengers cAMP, inositol phosphates and Ca 2+ on GH secretion were observed. The expression of gsp oncogenes was also studied.Results As usually reported, gsp oncogenes expressed in 6 of 18 tumors (33%). The effect of GHRP 6 and GHRH on cAMP production was observed in 11 tumors. GHRP 6 exerted no effect on cAMP production by gsp negative tumors, but stronger effect by 2 gsp positive tumors. Moreover, GHRP 6 potentiated the stimulation of cAMP production induced by GHRH in tumors without gsp oncogenes. GHRP 6 stimulated strongly GH secretion and PI turnover. The effects of GH secretion were reduced or abolished by inhibitors of protein kinase C (phloretin) and calmodulin (W7).Conclusion Intracellular multiple 'second messengers' might involve in the regulation of GH secretion.