Bennett P A, Thomas G B, Howard A D, Feighner S D, van der Ploeg L H, Smith R G, Robinson I C
Division of Neurophysiology, National Institute for Medical Research, London, United Kingdom.
Endocrinology. 1997 Nov;138(11):4552-7. doi: 10.1210/endo.138.11.5476.
Synthetic GH secretagogues (GHSs) act via a receptor (GHS-R) distinct from that for GH-releasing hormone (GHRH). We have studied the hypothalamic expression and regulation of this receptor by in situ hybridization using a homologous riboprobe for rat GHS-R. GHS-R mRNA is prominently expressed in arcuate (ARC) and ventromedial nuclei (VMN) and in hippocampus, but not in the periventricular nucleus. Little or no specific hybridization could be observed in the pituitary under the conditions that gave strong signals in the hypothalamus. No sex difference in GHS-R expression was found in ARC or hippocampus, though expression in VMN was lower in males than in females. Compared with GHRH and neuropeptide Y (NPY), GHS-R was expressed in a distinct region of ventral ARC, and in regions of VMN not expressing GHRH or NPY. GHS-R expression was highly sensitive to GH, being markedly increased in GH-deficient dw/dw dwarf rats, and decreased in dw/dw rats treated with bovine GH (200 microg/day) for 6 days. Similar changes were observed in GHRH expression, whereas NPY expression was reduced in dw/dw rats and increased by bGH treatment. Continuous sc infusion of GHRP-6 in normal female rats did not alter ARC or VMN GHS-R expression. Our data implicate ARC and VMN cells as major hypothalamic targets for direct GHS action. The sensitivity of ARC GHS-R expression to modulation by GH suggests that GHS-Rs may be involved in feedback regulation of GH.
合成生长激素促分泌素（GHSs）通过一种不同于生长激素释放激素（GHRH）受体的受体（GHS-R）发挥作用。我们使用大鼠GHS-R的同源核糖探针，通过原位杂交研究了该受体在下丘脑的表达及调控。GHS-R mRNA在弓状核（ARC）、腹内侧核（VMN）和海马中显著表达，但在室周核中不表达。在给予下丘脑强烈信号的条件下，垂体中几乎观察不到特异性杂交信号。在ARC或海马中未发现GHS-R表达存在性别差异，尽管VMN中的表达在雄性中低于雌性。与GHRH和神经肽Y（NPY）相比，GHS-R在腹侧ARC的一个不同区域以及不表达GHRH或NPY的VMN区域中表达。GHS-R表达对生长激素高度敏感，在生长激素缺乏的dw/dw侏儒大鼠中显著增加，而在用牛生长激素（200微克/天）处理6天的dw/dw大鼠中则降低。在GHRH表达中观察到类似变化，而NPY表达在dw/dw大鼠中降低，经bGH处理后增加。在正常雌性大鼠中持续皮下输注GHRP-6不会改变ARC或VMN中GHS-R的表达。我们的数据表明ARC和VMN细胞是下丘脑直接受GHS作用的主要靶点。ARC中GHS-R表达对生长激素调节的敏感性表明GHS-Rs可能参与生长激素的反馈调节。
