Miller T L, Mayo K E
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA.
Endocrinology. 1997 Jun;138(6):2458-65. doi: 10.1210/endo.138.6.5184.
Glucocorticoids regulate GH synthesis and secretion by influencing both hypothalamic and pituitary function. With respect to GH-releasing hormone (GHRH), an important GH secretagogue, glucocorticoids are reported not only to suppress hypothalamic GHRH expression but also to augment pituitary responsiveness to GHRH. To investigate further this latter observation, we have determined the effects of this steroid on expression of the GHRH receptor (GHRH-R) gene in the rat pituitary in vivo and in pituitary cells in vitro. Adult male rats were adrenalectomized or sham operated and treated with s.c. implants of cholesterol or corticosterone. Adrenalectomized animals showed substantially reduced pituitary GHRH-R mRNA levels, when compared with untreated sham-operated animals. Conversely, administration of corticosterone increased pituitary GHRH-R mRNA levels in intact, as well as adrenalectomized rats. We also analyzed the effects of the synthetic glucocorticoid, dexamethasone, on GHRH-R mRNA expression in cultured rat anterior pituitary cells. GHRH-R mRNA was significantly increased by dexamethasone, with a maximal response observed in the presence of 100 nM hormone. This dose of dexamethasone substantially elevated GHRH-R mRNA after 6 h, 12 h, and 24 h of treatment. Dexamethasone did not increase GHRH-R mRNA in the presence of the transcriptional inhibitor actinomycin D, indicating that the predominant effect of the hormone is to increase transcription of the GHRH-R gene. These data demonstrate that GHRH-R mRNA levels are directly stimulated by glucocorticoids, both in the presence and absence of hypothalamic influences, providing a probable explanation for the ability of this steroid to alter pituitary responsiveness to GHRH.
糖皮质激素通过影响下丘脑和垂体功能来调节生长激素（GH）的合成与分泌。关于生长激素释放激素（GHRH）这种重要的生长激素促分泌素，据报道糖皮质激素不仅会抑制下丘脑GHRH的表达，还会增强垂体对GHRH的反应性。为了进一步研究后一观察结果，我们已经确定了这种类固醇对大鼠垂体中GHRH受体（GHRH-R）基因在体内和体外垂体细胞中的表达的影响。成年雄性大鼠接受肾上腺切除术或假手术，并皮下植入胆固醇或皮质酮进行治疗。与未处理的假手术动物相比，肾上腺切除的动物垂体GHRH-R mRNA水平大幅降低。相反，给予皮质酮会增加完整大鼠以及肾上腺切除大鼠的垂体GHRH-R mRNA水平。我们还分析了合成糖皮质激素地塞米松对培养的大鼠垂体前叶细胞中GHRH-R mRNA表达的影响。地塞米松显著增加了GHRH-R mRNA，在存在100 nM激素的情况下观察到最大反应。在处理6小时、12小时和24小时后，这种剂量的地塞米松使GHRH-R mRNA大幅升高。在地塞米松存在转录抑制剂放线菌素D的情况下，它不会增加GHRH-R mRNA，这表明该激素的主要作用是增加GHRH-R基因的转录。这些数据表明，无论有无下丘脑的影响，糖皮质激素都会直接刺激GHRH-R mRNA水平，这为这种类固醇改变垂体对GHRH反应性的能力提供了一个可能的解释。
