Tamura H, Kamegai J, Sugihara H, Kineman R D, Frohman L A, Wakabayashi I
Department of Medicine, Nippon Medical School, Tokyo, Japan.
J Neuroendocrinol. 2000 Jun;12(6):481-5. doi: 10.1046/j.1365-2826.2000.00446.x.
Glucocorticoids regulate growth hormone (GH) secretion by modulating both hypothalamic and pituitary function. At the level of the pituitary, glucocorticoids increase GH and GH-releasing hormone receptor (GHRH-R) gene expression. To test if glucocorticoids might also regulate the pituitary expression of the recently identified GH secretagogue (GHS) receptor, GHS-R; adult male rats were adrenalectomized or sham operated, and treated with the synthetic glucocorticoid (dexamethasone, 200 microg/day) or vehicle for 8 days. Pituitary GHS-R mRNA levels were assessed by reverse transcriptase polymerase chain reaction (RT-PCR). Adrenalectomy decreased pituitary GHS-R mRNA to 45% of vehicle-treated, sham-operated rats (P < 0.05). Administration of dexamethasone increased GHS-R mRNA levels in sham-operated as well as in adrenalectomized rats (199 +/- 24% (P < 0.05) and 369 +/- 48% (P < 0.01) of vehicle-treated controls). Addition of dexamethasone to primary rat pituitary cell cultures increased GHS-R mRNA levels in a dose- and time-dependent manner while the transcriptional inhibitor, actinomycin D, completely blocked the stimulatory action of dexamethasone. Taken together, these results suggest glucocorticoids directly increase pituitary GHS-R mRNA levels by stimulating GHS-R gene transcription.
糖皮质激素通过调节下丘脑和垂体功能来调控生长激素(GH)的分泌。在垂体水平,糖皮质激素可增加GH和生长激素释放激素受体(GHRH-R)的基因表达。为了检测糖皮质激素是否也能调节最近发现的生长激素促分泌素(GHS)受体(GHS-R)在垂体中的表达,将成年雄性大鼠进行肾上腺切除术或假手术,并给予合成糖皮质激素(地塞米松,200微克/天)或赋形剂处理8天。通过逆转录聚合酶链反应(RT-PCR)评估垂体GHS-R mRNA水平。肾上腺切除术使垂体GHS-R mRNA水平降至接受赋形剂处理的假手术大鼠的45%(P<0.05)。给予地塞米松可使假手术大鼠和肾上腺切除大鼠的GHS-R mRNA水平升高(分别为接受赋形剂处理对照组的199±24%(P<0.05)和369±48%(P<0.01))。向原代大鼠垂体细胞培养物中添加地塞米松可使GHS-R mRNA水平呈剂量和时间依赖性增加,而转录抑制剂放线菌素D可完全阻断地塞米松的刺激作用。综上所述,这些结果表明糖皮质激素通过刺激GHS-R基因转录直接增加垂体GHS-R mRNA水平。