Korkor A, Martin K J, Olgaard K, Bergfeld M, Teitelbaum S, Klahr S, Slatopolsky E
Endocrinology. 1983 Aug;113(2):625-31. doi: 10.1210/endo-113-2-625.
The interaction between glucocorticoids (GC) and PTH has been suggested to play a role in the pathogenesis of GC-induced osteopenia. The present studies were designed to examine the effect of acute (5-h) or chronic (4-week) GC administration in vivo on 1) cAMP release by the isolated perfused dog tibia before (basal) and after the addition of synthetic bovine PTH-(1-34) [syn bPTH-(1-34)] (stimulated) to the perfusate in vitro, in the presence or absence of the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (IBMX; 1 mM), and 2) the percent arteriovenous difference of immunoreactive PTH across bone. Acute administration of 6 mg/kg methylprednisolone (MP) did not affect the basal release of cAMP from bone (6.9 +/- 1.6 pmol/min in control vs. 6.1 +/- 1.2 pmol/min in MP-treated animals); however, syn bPTH-(1-34) stimulated release of cAMP was higher in the MP-treated animals (45 +/- 8.1 pmol/min) than in controls (26.8 +/- 3.0 pmol/min). When IBMX was added to the perfusate, basal cAMP release was not different in control and MP-treated bone (17.2 +/- 2.1 pmol/min in control vs. 19.1 +/- 1.9 pmol/min in MP-treated bone), and syn bPTH-(1-34)-stimulated release of cAMP was equivalent in both groups. In contrast, chronic prednisone therapy lead to a decrease in both basal and PTH-stimulated release of cAMP from bone (3.1 +/- 0.4 and 6.9 +/- 1.6 pmol/min for basal, and 13.1 +/- 1.7 and 26.8 +/- 3.0 pmol/min for stimulated values, respectively). However, the percent changes from the basal levels were not different in the two groups. These results were correlated with histological studies of rib biopsies obtained from these animals, which showed evidence of osteopenia and decreased bone turnover. Neither acute nor chronic GC administration had any effect on arterio-venous differences for PTH across the bone. Thus, these studies demonstrate that 1) acute administration of MP enhances the response of bone to PTH, an effect that is not apparent in the presence of the phosphodiesterase inhibitor IBMX; and 2) chronic prednisone therapy decreased basal and PTH-stimulated cAMP release, an effect that correlated with histological evidence of decreased bone turnover.
糖皮质激素（GC）与甲状旁腺激素（PTH）之间的相互作用被认为在GC诱导的骨质减少的发病机制中起作用。本研究旨在检测体内急性（5小时）或慢性（4周）给予GC对以下方面的影响：1）在体外灌注液中添加合成牛PTH-（1-34）[合成bPTH-（1-34）]（刺激后）之前（基础状态）和之后，分离灌注的犬胫骨释放cAMP的情况，同时存在或不存在磷酸二酯酶抑制剂3-异丁基-1-甲基黄嘌呤（IBMX；1 mM）；2）骨中免疫反应性PTH的动静脉差异百分比。急性给予6 mg/kg甲泼尼龙（MP）不影响骨中cAMP的基础释放（对照组为6.9±1.6 pmol/min，MP处理组动物为6.1±1.2 pmol/min）；然而，MP处理组动物中合成bPTH-（1-34）刺激的cAMP释放高于对照组（45±8.1 pmol/min vs. 26.8±3.0 pmol/min）。当向灌注液中添加IBMX时，对照组和MP处理的骨中基础cAMP释放无差异（对照组为17.2±2.1 pmol/min，MP处理的骨为19.1±1.9 pmol/min），且两组中合成bPTH-（1-34）刺激的cAMP释放相当。相反，慢性泼尼松治疗导致骨中基础和PTH刺激的cAMP释放均减少（基础值分别为3.1±0.4和6.9±1.6 pmol/min，刺激值分别为13.1±1.7和26.8±3.0 pmol/min）。然而，两组中相对于基础水平的变化百分比无差异。这些结果与从这些动物获得的肋骨活检组织学研究相关，该研究显示有骨质减少和骨转换降低的证据。急性或慢性给予GC对骨中PTH的动静脉差异均无任何影响。因此，这些研究表明：1）急性给予MP可增强骨对PTH的反应，在存在磷酸二酯酶抑制剂IBMX时这种作用不明显；2）慢性泼尼松治疗降低基础和PTH刺激的cAMP释放，这种作用与骨转换降低的组织学证据相关。
