Activation of the hypothalamo-pituitary-adrenal axis by the growth hormone (GH) secretagogue, GH-releasing peptide-6, in rats
Activation of the hypothalamo-pituitary-adrenal axis by the growth hormone (GH) secretagogue, GH-releasing peptide-6, in rats
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DOI：
10.1210/en.138.4.1585
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发表时间：
1997-04-01
期刊：
影响因子：
4.8
通讯作者：
Robinson, ICAF
中科院分区：
文献类型：
--
作者：
Thomas, GB;Fairhall, KM;Robinson, ICAF
GH-释放六肽（GHRP-6）是一种合成促分泌剂，通过作用于下丘脑和垂体部位刺激GH的释放。ghrp也会引起少量但显著的血浆促肾上腺皮质激素和肾上腺激素浓度的增加。由于这些分泌剂不直接释放ACTH，它们可能与控制ACTH释放的下丘脑肽能系统相互作用，如CRH和精氨酸加压素（AVP）。我们现在已经检查了清醒大鼠的下丘脑-垂体-肾上腺轴被GHRP-6激活。在一系列实验中，给大鼠静脉注射10 μ g GHRP-6、2 μ g CRH、0.5 μ g AVP或生理盐水，单独或联合注射，并抽取一系列血浆样本，检测ACTH、皮质酮和GH。CRH和AVP增加了所有大鼠的血浆ACTH水平，而ACTH和皮质酮对GHRP-6的反应是可变的，并且依赖于下丘脑-垂体-肾上腺轴的普遍活性。在GHRP-6给药前血浆ACTH和皮质酮水平最低的大鼠中，GHRP-6刺激的ACTH反应最大。GHRP-6联合CRH并不比单独使用CRH时增加ACTH水平（ACTH变化，1570 +/- 207us）。1714 +/- 245 pg/ml)，而与AVP单独作用相比，GHRP-6和AVP联合作用显著增加ACTH水平（ACTH变化5587 +/- 669 us）。2338 +/- 451 pg/ml；P < 0.05)。血浆ACTH和皮质酮水平较低的大鼠GH对GHRP-6的反应明显高于ACTH和皮质酮水平升高的大鼠（GH反应变化，119 +/- 27 vs 29 +/- 7 ng/ml, P < 0.01）。单独的CRH显著抑制生长激素的释放。crh后40 min， 11.9 +/- 3.8 vs. 1.7 +/- 0.4 ng/ml；P < 0.05)，而AVP对生长激素水平无影响。CRH和AVP对GH对GHRP-6的反应均无影响。我们认为GHRP-6通过下丘脑介导ACTH的释放，这些作用可能至少部分通过内源性CRH的释放介导，并受循环糖皮质激素的调节。
GH-releasing hexapeptide (GHRP-6) is a synthetic secretagogue that stimulates the release of GH by acting at both hypothalamic and pituitary sites. GHRPs also consistently elicit small, but significant, increases in plasma concentrations of ACTH and adrenal steroids. As these secretagogues do not release ACTH directly, they probably interact with the hypothalamic peptidergic systems controlling ACTH release, such as CRH and arginine vasopressin (AVP). We have now examined the activation of the hypothalamo-pituitary-adrenal axis by GHRP-6 in conscious rats. In a series of experiments, rats were injected iv with 10 mu g GHRP-6, 2 mu g CRH, 0.5 mu g AVP, or saline, alone or in combination, and serial plasma samples withdrawn and assayed for ACTH, corticosterone, and GH. CRH and AVP increased plasma ACTH levels in all rats, whereas ACTH and corticosterone responses to GHRP-6 were variable and were dependent on the prevailing activity of the hypothalamo-pituitary-adrenal axis. GHRP-6 stimulated the largest ACTH responses in rats that had the lowest basal plasma ACTH and corticosterone levels before GHRP-6 administration. GHRP-6 given in combination with CRH did not increase ACTH levels beyond the response to CRH alone (change in ACTH, 1570 +/- 207 us. 1714 +/- 245 pg/ml), whereas the combination of GHRP-6 and AVP markedly increased ACTH levels compared with the effects of AVP alone (change in ACTH, 5587 +/- 669 us. 2338 +/- 451 pg/ml; P < 0.05). The GH responses to GHRP-6 were significantly greater in rats with low basal plasma ACTH and corticosterone levels than in rats with elevated ACTH and corticosterone levels (change in GH response, 119 +/- 27 vs. 29 +/- 7 ng/ml;P < 0.01). CRH alone significantly inhibited GH release (pre- us. 40 min post-CRH, 11.9 +/- 3.8 vs. 1.7 +/- 0.4 ng/ml; P < 0.05), whereas AVP alone had no effect on GH levels. Neither CRH nor AVP had any effect on the GH response to GHRP-6. We suggest that GHRP-6 acts via the hypothalamus to mediate the release of ACTH, and that these effects are probably mediated at least in part via the release of endogenous CRH and are subject to regulation by circulating glucocorticoids.