Department of Pharmacology and Medical Research Center for Bioreaction to ROS and Biomedical Science Institute, Kyunghee University School of Medicine, Seoul 130-701, Korea.
Korean J Physiol Pharmacol. 2008 Oct;12(5):217-23. doi: 10.4196/kjpp.2008.12.5.217. Epub 2008 Oct 31.
To directly test if elevated glucocorticoids are required for fasting-induced regulation of growth hormone (GH)-releasing hormone (GHRH), GHRH receptors (GHRH-R) and ghrelin receptors (GHS-R) expression, male rats were bilaterally adrenalectomized or sham operated. After 7 days, animals were fed ad libitum or fasted for 48 h. Bilateral adrenalectomy increased hypothalamic GHRH to 146% and decreased neuropeptide Y (NPY) mRNA to 54% of SHAM controls. Pituitary GHRH-R and GHS-R mRNA levels were decreased by adrenalectomy to 30% and 80% of sham-operated controls. In shamoperated rats, fasting suppressed hypothalamic GHRH (49%) and stimulated NPY (166%) mRNA levels, while fasting increased pituitary GHRH-R (391%) and GHS-R (218%) mRNA levels. However, in adrenalectomized rats, fasting failed to alter pituitary GHRH-R mRNA levels, while the fasting-induced suppression of GHRH and elevation of NPY and GHS-R mRNA levels remained intact. In fasted adrenalectomized rats, corticosterone replacement increased GHRH-R mRNA levels and intensified the fasting-induced decrease in GHRH, but did not alter NPY or GHS-R response. These data suggest that elevated glucocorticoids mediate the effects of fasting on hypothalamic GHRH and pituitary GHRH-R expression, while glucocorticoids are likely not the major determinant in fasting-induced increases in hypothalamic NPY and pituitary GHS-R expression.
为了直接测试升高的糖皮质激素是否是禁食诱导生长激素释放激素（GHRH）、GHRH 受体（GHRH-R）和 ghrelin 受体（GHS-R）表达调节所必需的，雄性大鼠接受双侧肾上腺切除术或假手术。7 天后，动物自由进食或禁食 48 小时。双侧肾上腺切除术使下丘脑 GHRH 增加到对照 SHAM 的 146%，并使神经肽 Y（NPY）mRNA 减少到对照 SHAM 的 54%。垂体 GHRH-R 和 GHS-R mRNA 水平分别减少到对照 SHAM 的 30%和 80%。在对照 SHAM 大鼠中，禁食抑制下丘脑 GHRH（49%）并刺激 NPY（166%）mRNA 水平，而禁食增加垂体 GHRH-R（391%）和 GHS-R（218%）mRNA 水平。然而，在肾上腺切除大鼠中，禁食未能改变垂体 GHRH-R mRNA 水平，而禁食诱导的 GHRH 抑制和 NPY 和 GHS-R mRNA 水平升高仍然存在。在禁食的肾上腺切除大鼠中，皮质酮替代增加了 GHRH-R mRNA 水平并加剧了禁食诱导的 GHRH 减少，但没有改变 NPY 或 GHS-R 反应。这些数据表明，升高的糖皮质激素介导了禁食对下丘脑 GHRH 和垂体 GHRH-R 表达的影响，而糖皮质激素可能不是禁食诱导下丘脑 NPY 和垂体 GHS-R 表达增加的主要决定因素。
