Chan Y Y, Steiner R A, Clifton D K
Department of Medicine, University of Washington School of Medicine, Seattle, 98195, USA.
Endocrinology. 1996 Apr;137(4):1319-25. doi: 10.1210/endo.137.4.8625906.
GH is thought to exert a short-loop feedback action on the hypothalamic somatostatin- and GH-releasing hormone (GHRH)-containing neurons. The direct actions of GH are mediated through GH receptors. In the male rat, few GHRH-containing neurons in the arcuate nucleus (ARC) appear to express the GH receptor messenger RNA (mRNA); however, some unidentified neurons near GHRH neurons do. Recent evidence suggests that neuropeptide-Y (NPY)-containing neurons, which are located near GHRH neurons in the ARC, are targets for GH action because treatment of rats with GH induces c-fos expression in these cells. We conducted two experiments to test the hypothesis that GH acts on NPY neurons in the ARC. First, we performed double-label in situ hybridization to determine whether NPY neurons in the ARC express GH receptor mRNA. Second, we investigated the possibility that GH regulates NPY mRNA expression by using in situ hybridization to compare ARC NPY mRNA levels among groups of normal (n = 7), hypophysectomized (n = 7), and hypophysectomized/rGH-treated (1.5 mg rat GH over 3 days; n = 6) rats. We found that most of the NPY-containing neurons in the ARC expressed GH receptor mRNA, whereas hypothalamic NPY neurons residing outside of the ARC did not. Furthermore, hypophysectomy significantly decreased NPY mRNA levels, and GH treatment restored the levels to those of the intact animals. We conclude that GH regulates the activity of NPY neurons in the ARC by a direct action on GH receptors that are expressed by NPY neurons. Whether the action of GH on NPY neurons in the ARC is related to the feedback control of GH secretion or some other physiological function remains to be determined.
生长激素（GH）被认为对下丘脑含有生长抑素和生长激素释放激素（GHRH）的神经元发挥短环反馈作用。GH 的直接作用通过 GH 受体介导。在雄性大鼠中，弓状核（ARC）中少数含有 GHRH 的神经元似乎表达 GH 受体信使核糖核酸（mRNA）；然而，GHRH 神经元附近一些未明确身份的神经元则表达。最近的证据表明，位于 ARC 中 GHRH 神经元附近的含神经肽 Y（NPY）的神经元是 GH 作用的靶点，因为用 GH 处理大鼠会诱导这些细胞中 c-fos 表达。我们进行了两项实验来检验 GH 作用于 ARC 中 NPY 神经元这一假说。首先，我们进行了双重标记原位杂交，以确定 ARC 中的 NPY 神经元是否表达 GH 受体 mRNA。其次，我们通过原位杂交比较正常（n = 7）、垂体切除（n = 7）以及垂体切除/重组人生长激素（rGH）处理（3 天内给予 1.5 mg 大鼠 GH；n = 6）大鼠组之间 ARC 的 NPY mRNA 水平，研究 GH 调节 NPY mRNA 表达的可能性。我们发现，ARC 中大多数含 NPY 的神经元表达 GH 受体 mRNA，而位于 ARC 外的下丘脑 NPY 神经元则不表达。此外，垂体切除显著降低了 NPY mRNA 水平，而 GH 处理使这些水平恢复到完整动物的水平。我们得出结论，GH 通过直接作用于 NPY 神经元表达的 GH 受体来调节 ARC 中 NPY 神经元的活性。GH 对 ARC 中 NPY 神经元的作用是否与 GH 分泌的反馈控制或其他某些生理功能相关，仍有待确定。
