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体外给予生长激素释放激素(GHRH)和生长激素释放肽-2(GHRP-2)对绵羊垂体细胞生长激素(GH)分泌以及GH、垂体转录因子-1、GHRH受体、生长激素促分泌素受体和生长抑素受体mRNA水平的影响。

Effect of GHRH and GHRP-2 treatment in vitro on GH secretion and levels of GH, pituitary transcription factor-1, GHRH-receptor, GH-secretagogue-receptor and somatostatin receptor mRNAs in ovine pituitary cells.

作者信息

Yan Ming, Hernandez Maria, Xu Ruwei, Chen Chen

机构信息

Prince Henry's Institute of Medical Research, Clayton, Victoria 3168, Australia.

出版信息

Eur J Endocrinol. 2004 Feb;150(2):235-42. doi: 10.1530/eje.0.1500235.

Abstract

OBJECTIVE

Growth hormone (GH)-releasing hormone (GHRH) and GH-releasing peptides (GHRPs) stimulate the release of GH through their specific receptors on somatotropes. Combined GHRH and GHRP administration causes a synergistic GH release in vivo by an unknown mechanism. The current study focuses on the direct action of GHRH and GHRP on several molecular targets in somatotropes.

DESIGN AND METHODS

To clarify the mechanism of action, ovine somatotropes were used to measure the expression of mRNAs encoding for GH, pituitary transcription factor-1 (Pit-1), GH-secretagogue receptor (GHS-R), GHRH-R, somatostatin receptor subtypes (sst-1 and sst-2) and GH release after GHRH and GHRP-2 treatment for 0.5, 1, 1.5 and 2 h.

RESULTS

GHRH (10 nM), GHRP-2 (100 nM) and combined GHRH-GHRP-2 increased the levels of GH mRNA and GH release from 0.5 to 2 h in a time-dependent manner. The levels of Pit-1, GHRH-R and GHS-R mRNA were increased after 0.5 h treatment of cells with GHRH and GHRP-2. The levels of sst-1 but not sst-2 mRNA were significantly increased after 0.5 and 1 h of GHRH treatment. In contrast, both sst-1 and sst-2 mRNA expression was inhibited after 0.5-2 h of GHRP treatment.

CONCLUSIONS

These data demonstrate a direct in vitro modification of ovine somatotropes by GHRH and GHRP-2 resulting in altered GHRH-R, GHS-R, Pit-1, sst-1, sst-2 and GH gene expression; this may underlie the regulatory action of GHRH and GHRP-2 on GH secretion.

摘要

目的

生长激素(GH)释放激素(GHRH)和生长激素释放肽(GHRPs)通过其在生长激素细胞上的特异性受体刺激GH释放。联合给予GHRH和GHRP在体内可通过未知机制引起协同性GH释放。本研究聚焦于GHRH和GHRP对生长激素细胞中几个分子靶点的直接作用。

设计与方法

为阐明作用机制,采用绵羊生长激素细胞来测量经GHRH和GHRP - 2处理0.5、1、1.5和2小时后,编码GH、垂体转录因子 - 1(Pit - 1)、生长激素促分泌素受体(GHS - R)、GHRH受体(GHRH - R)、生长抑素受体亚型(sst - 1和sst - 2)的mRNA表达以及GH释放情况。

结果

GHRH(10 nM)、GHRP - 2(100 nM)以及联合使用GHRH - GHRP - 2可使GH mRNA水平和GH释放在0.5至2小时内呈时间依赖性增加。用GHRH和GHRP - 2处理细胞0.5小时后,Pit - 1、GHRH - R和GHS - R mRNA水平升高。GHRH处理0.5和1小时后,sst - 1而非sst - 2 mRNA水平显著升高。相反,GHRP处理0.5至2小时后,sst - 1和sst - 2 mRNA表达均受到抑制。

结论

这些数据表明GHRH和GHRP - 2对绵羊生长激素细胞具有直接的体外修饰作用,导致GHRH - R、GHS - R、Pit - 1、sst - 1、sst - 2和GH基因表达改变;这可能是GHRH和GHRP - 2对GH分泌进行调节作用的基础。

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