DEXAMETHASONE INCREASES GROWTH-HORMONE RECEPTOR MESSENGER-RIBONUCLEIC-ACID LEVELS IN LIVER AND GROWTH-PLATE
DEXAMETHASONE INCREASES GROWTH-HORMONE RECEPTOR MESSENGER-RIBONUCLEIC-ACID LEVELS IN LIVER AND GROWTH-PLATE
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DOI：
10.1210/en.135.3.1113
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发表时间：
1994-09-01
期刊：
影响因子：
4.8
通讯作者：
BARON, J
中科院分区：
文献类型：
--
作者：
HEINRICHS, C;YANOVSKI, JA;BARON, J
糖皮质激素抑制线性生长，并使靶组织，特别是肝脏和生长板，对GH不敏感。我们推测，糖皮质激素诱导的GH不敏感性是由于GH受体在信使RNA（mRNA）水平的基因表达减少。为了验证这一假设，我们给4.5周龄雄性家兔（每组n = 6-9）ip地塞米松或溶剂，并测量GH受体mRNA水平（通过RNA酶保护试验）和血清GH结合蛋白水平（通过放射免疫沉淀试验）。相反，观察到GH受体mRNA水平的组织特异性刺激。该效应的剂量-反应关系是双相的，因为较低的生长抑制剂量的地塞米松（0.1 mg/kg.day）引起GH受体mRNA水平的较大增加，而较高的生长抑制剂量（4 mg/kg.天）具有较小的效应。在生长板和肝脏（对线性生长重要的靶组织）中观察到地塞米松诱导的GH受体mRNA增加，但在肾脏中未观察到。血清GH结合蛋白水平也显示出对地塞米松治疗的刺激反应，具有双相剂量反应关系。这些数据表明，糖皮质激素诱导的GH不敏感性不能解释为GH受体mRNA水平下降。相反，地塞米松引起GH受体mRNA水平的组织特异性刺激，具有双相剂量-反应关系。
Glucocorticoid inhibits linear growth and renders target tissues, particularly liver and growth plate, insensitive to GH. We hypothesized that glucocorticoid-induced GH insensitivity is due to decreased gene expression of the GH receptor at the messenger RNA (mRNA) level. To test this hypothesis, we treated 4.5-wk-old male rabbits (n = 6-9 per group) with ip dexamethasone or vehicle and measured GH receptor mRNA levels (by RNase protection assay) and serum GH-binding protein levels (by radioimmunoprecipitation assay).Contrary to our hypothesis, dexamethasone administered in growth-suppressing doses did not decrease GH receptor mRNA levels in liver or growth plate. Instead a tissue-specific stimulation of GH receptor mRNA levels was observed. The dose-response relationship of this effect was biphasic, since the lower growth-suppressing dose of dexamethasone (0.1 mg/kg.day) caused the greater increase in GH receptor mRNA levels, whereas the higher growth-suppressing dose (4 mg/kg.day) had less effect. The dexamethasone-induced increase in GH receptor mRNA was observed in growth plate and liver, target tissues important for linear growth, but not in kidney. Serum GH-binding protein levels also showed a stimulatory response to dexamethasone treatment, with a biphasic dose-response relationship.These data suggest that glucocorticoid-induced GH insensitivity cannot be explained by decreased GH receptor mRNA levels. To the contrary, dexamethasone causes a tissue-specific stimulation in GH receptor mRNA levels with a biphasic dose-response relationship.