Thomas G B, Fairhall K M, Robinson I C
Division of Neurophysiology, National Institute for Medical Research, London, United Kingdom.
Endocrinology. 1997 Apr;138(4):1585-91. doi: 10.1210/endo.138.4.5065.
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 i.v. with 10 microg GHRP-6, 2 microg CRH, 0.5 microg AVP, or saline, alone or in combination, and serial plasma samples withdrawn and assayed for ACTH, corticosterone, and GH.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 vs. 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 vs. 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- vs. 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.
生长激素释放六肽（GHRP - 6）是一种合成促分泌素，它通过作用于下丘脑和垂体部位来刺激生长激素的释放。GHRP还能持续引起促肾上腺皮质激素（ACTH）和肾上腺类固醇血浆浓度的小幅但显著升高。由于这些促分泌素并不直接释放ACTH，它们可能与控制ACTH释放的下丘脑肽能系统相互作用，如促肾上腺皮质激素释放激素（CRH）和精氨酸加压素（AVP）。我们现在研究了GHRP - 6对清醒大鼠下丘脑 - 垂体 - 肾上腺轴的激活作用。在一系列实验中，给大鼠静脉注射10微克GHRP - 6、2微克CRH、0.5微克AVP或生理盐水，单独注射或联合注射，然后采集系列血浆样本并检测ACTH、皮质酮和生长激素。CRH和AVP在所有大鼠中均升高了血浆ACTH水平，而ACTH和皮质酮对GHRP - 6的反应是可变的，并且取决于下丘脑 - 垂体 - 肾上腺轴的当前活性。在给予GHRP - 6之前基础血浆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与CRH联合使用时，ACTH水平的升高并未超过单独使用CRH时的反应（ACTH变化值，1570±207对1714±245皮克/毫升），而GHRP - 6与AVP联合使用时，与单独使用AVP相比，ACTH水平显著升高（ACTH变化值，5587±669对2338±451皮克/毫升；P<0.05）。基础血浆ACTH和皮质酮水平低的大鼠对GHRP - 6的生长激素反应显著大于ACTH和皮质酮水平升高的大鼠（生长激素反应变化值，119±27对29±7纳克/毫升；P<0.01）。单独使用CRH显著抑制生长激素释放（注射CRH前与注射后40分钟相比，11.9±3.8对1.7±0.4纳克/毫升；P<0.05），而单独使用AVP对生长激素水平无影响。CRH和AVP对GHRP - 6的生长激素反应均无任何影响。我们认为GHRP - 6通过下丘脑介导ACTH的释放，并且这些作用可能至少部分通过内源性CRH的释放介导，并且受循环糖皮质激素的调节。
