Señarís R M, Lago F, Coya R, Pineda J, Diéguez C
Department of Physiology, Faculty of Medicine, University of Santiago de Compostela, Spain.
Endocrinology. 1996 Dec;137(12):5236-41. doi: 10.1210/endo.137.12.8940340.
Although it is well known that chronic treatment with glucocorticoids inhibits somatic growth, the mechanism of action of this inhibitory effect is not completely understood. It is likely that glucocorticoids act at various levels, including pituitary, hypothalamus, and peripheral organs modulating GH synthesis, secretion, and action. In this work, we evaluated the effect of dexamethasone on hypothalamic somatostatin and GH-releasing hormone (GHRH) messenger RNA (mRNA) levels by in situ hybridization. We found a significant decrease of somatostatin mRNA content in the periventricular nucleus of the hypothalamus after 3, 8, and 15 days of treatment with dexamethasone. Furthermore, we observed a reduction in GHRH mRNA levels in the arcuate nucleus after 8 and 15 days of treatment with this steroid. As it has been shown that GH feeds back to regulate somatostatin and GHRH expression at the hypothalamic level through high affinity GH receptors, we evaluated the possibility of a GH-mediated action in the inhibitory effect of glucocorticoids on somatostatin and GHRH mRNA levels. To address this issue, we first studied the GH receptor mRNA content in both the periventricular and arcuate nuclei of the hypothalamus after dexamethasone treatment. Secondly, the effect of dexamethasone on somatostatin and GHRH mRNA levels in hypophysectomized animals also was assessed. We found a significant decrease in GH receptor mRNA levels in the periventricular nucleus and in the arcuate nucleus after 1, 3, 8, and 15 days of glucocorticoid administration. Finally, in hypophysectomized rats, dexamethasone treatment for 15 days did not reduce somatostatin mRNA levels in the periventricular nucleus but significantly decreased GHRH mRNA content in the arcuate nucleus. In summary, our results suggest an inhibitory GH-mediated effect of dexamethasone on somatostatin mRNA levels in the periventricular nucleus and an inhibitory direct effect of dexamethasone on GHRH neurones in the arcuate nucleus.
虽然众所周知，长期使用糖皮质激素会抑制躯体生长，但其抑制作用的作用机制尚未完全明了。糖皮质激素可能在多个水平发挥作用，包括垂体、下丘脑以及调节生长激素（GH）合成、分泌和作用的外周器官。在本研究中，我们通过原位杂交评估了地塞米松对下丘脑生长抑素和生长激素释放激素（GHRH）信使核糖核酸（mRNA）水平的影响。我们发现，用地塞米松处理3天、8天和15天后，下丘脑室周核中生长抑素mRNA含量显著降低。此外，用该类固醇处理8天和15天后，我们观察到弓状核中GHRH mRNA水平降低。由于已经表明GH通过高亲和力的GH受体在下丘脑水平反馈调节生长抑素和GHRH的表达，我们评估了GH介导的作用在糖皮质激素对生长抑素和GHRH mRNA水平抑制作用中的可能性。为了解决这个问题，我们首先研究了地塞米松处理后下丘脑室周核和弓状核中GH受体mRNA的含量。其次，还评估了地塞米松对垂体切除动物生长抑素和GHRH mRNA水平的影响。我们发现，给予糖皮质激素1天、3天、8天和15天后，室周核和弓状核中GH受体mRNA水平显著降低。最后，在垂体切除的大鼠中，地塞米松处理15天并未降低室周核中生长抑素mRNA水平，但显著降低了弓状核中GHRH mRNA含量。总之，我们的结果表明，地塞米松对室周核中生长抑素mRNA水平具有由GH介导的抑制作用，而对地塞米松对弓状核中GHRH神经元具有直接抑制作用。
