Multiple intracellular signallings involved in regulation of on channels by GH releasing or inhibitory hormones in pituitary somatotropes

Influx of Ca2-via Ca2+ channels is the major step triggering exocytosis of pituitary somatotropes to release growth hormone (GH). Voltage-gated Ca2+ and K+ channels, the primary determinants of the influx of Ca2+ in somatotropes, are regulated by GH-releasing hornone (GHRH) and somatostatin (SRIF) through G protein-coupled signalling systems. Using whole-cell patch-clamp techniques, the changes of the Ca2+ and K+ currents in primary cultured somatotropes were recorded and signalling systems were studied using pharmacological reagents and intracellular dialysis of non-permeable molecules including antibodies and antisense oligonucleotides. GHRH increased both L-and T-types Ca2+ currents and decreased transient (I4) and delayed rectified (Ik) K+ currents. The increase in Ca2+ currents by GHRH was mediated by cAMP/protein kinase A system but the decrease in K+ currents required normal function of protein kinase C system. The GHRH-induced alteration of Ca2+ and K+ currents augments the influx of Ca2+ , leading to an increase in the [ Ca2+ ]I and the GH secretion. In contrary, a significant reduction in Ca2+ currents and increase in K currents were obtained in response to SRIF. The ion channel response to SRIF was demonstrated as a membrane delimited pathway and can be recorded by classic whole-cell configuration, Intracellular dialysis of anti-αi3 antibodies attenuated the increase in K + currents by SRIF whereas anti-αo antibodies blocked the reduction in the Ca2+ current by SRIF. Dialysis of antisense oligonucleotides specific for αo2 sub-units also attenuated the inhibition of SRIF on the Ca2+current. The Gi3 protein mediated the increase in K + currents and the Go2 protein mediated the reduction in the Ca2 +current by SRIF. The SRIF-induced alteration of Ca2 + and K + currents diminished the influx of Ca2+ , leading to a decrease in the [ Ca2+ ]I and the GH secretion. It is therefore concluded that multiple signalling systems are employed in the ion channel response to GHRH or SRIF in somatotropes, which leads to an increase or decrease in the GH secretion.     

牛生长激素释放激素基因研究进展

利用26篇文献,从GHRH基因的结构、生物学功能、多态性与生产性状的关系等方面就牛GHRH基因研究进展进行了论述.     

TPA增强gsp癌基因阳性人垂体生长激素腺瘤GHRP促生长激素分泌的效应

探讨细胞内ＰＫＣ信号传导系统在人垂体生长激素腺瘤ＧＨ分泌中的作用。方法：采用ＰＣＲ和直接序列分析法评价１０例肢端肥大症患者肿瘤组织的ｇｓｐ癌基因的表达。肿瘤组织取自手术切除标本，作细胞培养，进行体外生长激素释放激素（ＧＨＲＨ）和蛋白激酶Ｃ激活剂ＴＰＡ对ＧＨ释放效应研究。结果：１０例病人中有３例（３０％）为ｇｓｐ癌基因表达阳性，ＧＨＲＨ对ＧＨ刺激效应在本组中有２例表现出有统计学意义，ｇｓｐ阴性组７例中有４例表现出有统计学意义的刺激效应。ＴＰＡ可增强ＧＨＲＨ对ｇｓｐ阳性表达腺瘤细胞分泌的刺激作用，但是对阴性组细胞无此作用。结论：推测ＧＨＲＨ对ＧＨ的分泌效应除受腺苷酸环化酶－ｃＡＭＰ－蛋白激酶Ａ第二信使系统的调节外，尚有蛋白激酶Ｃ信号系统存在，可能与细胞间多信号传导系统的交叉通讯有关