Department of Physiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 105, Beer-Sheva 84105, Israel.
Eur Respir J. 2011 Oct;38(4):870-7. doi: 10.1183/09031936.00197610. Epub 2011 Mar 15.
Upper airway obstruction (UAO) can lead to abnormal growth hormone (GH) homeostasis and growth retardation but the mechanisms are unclear. We explored the effect of UAO on hypothalamic GH-releasing hormone (GHRH), which has a role in both sleep and GH regulation. The tracheae of 22-day-old rats were narrowed; UAO and sham-operated animals were sacrificed 16 days post-surgery. To stimulate slow-wave sleep (SWS) and GH secretion, rats were treated with ritanserin (5-HT(2) receptor antagonist). Sleep was measured with a telemetric system. Hypothalamic GHRH, hypothalamic GHRH receptor (GHRHR) and GH receptor, and orexin were analysed using ELISA, real-time PCR and Western blot. UAO decreased hypothalamic GHRH, GHRHR and GH receptor levels, while orexin mRNA increased (p<0.01). In UAO rats, the duration of wakefulness was elevated and the duration of SWS, paradoxical sleep and slow-wave activity was reduced (p<0.001). Ritanserin alleviated these effects, i.e. normalised hypothalamic GHRH content, decreased wake duration, increased duration and depth of SWS, and attenuated growth impairment (p<0.001). Here, we present evidence that growth retardation in UAO is associated with a reduction in hypothalamic GHRH content. Our findings show that abnormalities in the GHRH/GH axis underlie both growth retardation and SWS-disorder UAO.
上呼吸道阻塞 (UAO) 可导致生长激素 (GH) 稳态异常和生长迟缓，但机制尚不清楚。我们探讨了 UAO 对下丘脑生长激素释放激素 (GHRH) 的影响，GHRH 在睡眠和 GH 调节中都有作用。22 日龄大鼠的气管变窄；UAO 和假手术动物在手术后 16 天被处死。为了刺激慢波睡眠 (SWS) 和 GH 分泌，大鼠用利坦色林（5-HT2 受体拮抗剂）处理。使用遥测系统测量睡眠。使用 ELISA、实时 PCR 和 Western blot 分析下丘脑 GHRH、下丘脑 GHRH 受体 (GHRHR) 和 GH 受体以及食欲素。UAO 降低了下丘脑 GHRH、GHRHR 和 GH 受体水平，而食欲素 mRNA 增加（p<0.01）。在 UAO 大鼠中，觉醒持续时间升高，SWS、异相睡眠和慢波活动持续时间减少（p<0.001）。利坦色林减轻了这些影响，即正常化下丘脑 GHRH 含量，减少觉醒持续时间，增加 SWS 持续时间和深度，并减弱生长受损（p<0.001）。在这里，我们提供的证据表明，UAO 中的生长迟缓与下丘脑 GHRH 含量减少有关。我们的研究结果表明，GHRH/GH 轴的异常是 UAO 中生长迟缓和 SWS 障碍的基础。
