Administration of a nonpeptidyl growth hormone secretagogue, L-163, 255, changes somatostatin pattern, but has no effect on patterns of growth hormone-releasing factor in the hypophyseal-portal circulation of the conscious pig.

J. Drisko, T. Faidley, D. Zhang, T. McDonald, S. Nicolich, D. Hora, P. Cunningham, C. Li, E. Rickes, L. Mcnamara, C. Chang, R. Smith, G. Hickey
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引用次数: 14

Abstract

The activity of the growth hormone secretagog, L-163,255, on growth hormone (GH), growth hormone-releasing factor (GRF), and somatostatin (SRIF) levels was evaluated in a porcine model of hypophyseal portal blood (HPB) collection. Young, castrated pigs had HPB and jugular blood collected for approximately 300 min. The blood collection was divided into discrete periods: baseline (BL) approximately 180 min; GH response period (RSP) approximately 90 min; and positive control period following a GRF bolus, 30 min. RSP was divided into a dominant response period (DOM) and a tail (TL). The spontaneous relationship between HPB GRF and SRIF and peripheral GH during BL has been reported (Proc Soc Exp Biol Med 217:188-196, 1998). The apex of the GH pulse resulting from L-163,255 administration was nonrandomly associated (P < 0.05) with descending periods of SRIF troughs. Frequency and amplitude of GRF and SRIF pulses, and frequency and depth of SRIF troughs were not different between BL and the beginning of DOM (the 20-30 min of GH increase). GH AUC was significantly greater (P < 0.05) for DOM compared to BL and TL, and for TL compared to BL. GRF AUC tended to be greater (P < 0.1) for RSP compared to BL, but the majority of the increase was in the TL period. There were no significant differences in the SRIF AUCs between the sampling periods. Furthermore, in a separate experiment, fos activity (a marker of neuronal activation) in the hypothalamus of pigs was examined after either L-163,255 (1x or 4x), isotonic saline (control), or hypertonic saline (positive control) administration. There were no differences in fos activity in the GRF, SRIF, or CRH immunopositive neurons between L-163,255 treatment and control. The pituitaries of the L-163,255-treated pigs showed marked fos activation compared to the controls. In conclusion, L-163,255 in pigs has its primary effect at the level of the anterior pituitary.
非肽基生长激素促分泌剂l- 163,255可以改变生长抑素模式,但对有意识猪垂体-门静脉循环中生长激素释放因子的模式没有影响。
在猪垂体门静脉血(HPB)采集模型中,研究了生长激素分泌标记物L-163,255对生长激素(GH)、生长激素释放因子(GRF)和生长抑素(SRIF)水平的影响。阉割的幼猪进行HPB和颈静脉采血约300分钟。采血分为几个时间段:基线(BL)约180分钟;GH反应时间(RSP)约90 min;RSP分为显性反应期(DOM)和尾部反应期(TL)。BL期间HPB GRF和SRIF与外周血GH的自发关系已被报道(Proc Soc Exp Biol Med 217:188- 196,1998)。L-163,255引起的GH脉冲顶点与SRIF波谷下降周期呈非随机相关(P < 0.05)。GRF和SRIF脉冲的频率和幅度以及SRIF波谷的频率和深度在BL和DOM开始(GH增加20-30 min)之间没有差异。DOM的GH AUC显著高于BL和TL (P < 0.05), TL的GRF AUC显著高于BL (P < 0.1), RSP的GRF AUC倾向于高于BL (P < 0.1),但大部分增加发生在TL期。在采样周期之间,SRIF auc没有显著差异。此外,在另一项单独的实验中,在给药L-163,255(1倍或4倍)、等渗盐水(对照组)或高渗盐水(阳性对照组)后,检测猪下丘脑fos活性(神经元激活的标记物)。在L-163,255处理和对照组之间,GRF、SRIF或CRH免疫阳性神经元中的fos活性没有差异。与对照组相比,l -163,255处理的猪垂体显示明显的fos激活。综上所述,L-163,255对猪的主要影响是在垂体前叶水平。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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