Effect of 17beta-hydroxysteroid dehydrogenase type 2 inhibitor on bone strength in ovariectomized cynomolgus monkeys.
Effect of 17beta-hydroxysteroid dehydrogenase type 2 inhibitor on bone strength in ovariectomized cynomolgus monkeys.
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17β-羟基类固醇脱氢酶 2 型抑制剂对去卵巢食蟹猴骨强度的影响。
DOI：
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发表时间：
2008
影响因子：
1.9
通讯作者：
B. Dixon
中科院分区：
文献类型：
--
作者：
Bagi Cm;J. Wood;D. Wilkie;B. Dixon
在两种性别中，随着年龄的增长，性类固醇产生的减少会损害肌肉骨骼系统。我们研究的目的是测试WH-9062（一种新型17 β-羟基类固醇脱氢酶2型酶的非甾体小分子抑制剂）维持或改善骨强度而不升高血清睾酮或雌二醇水平的能力。将具有密封生长板的成熟雌性食蟹猴分为六组：假手术对照、OVX对照、OVX+倍美力（15 mg/kg/d）和接受1、5和25 mg/kg/d WH-9062的三组OVX猴。所有治疗均通过每日口服给药给药，持续23周。用WH-9062纠正OVX引起的脂质谱变化，包括降低总胆固醇和非HDL胆固醇，并维持HDL胆固醇的初始血浆水平。相对于OVX对照，仅最高剂量的WH-9062降低骨吸收。骨特异性碱性磷酸酶、骨钙素、BMC和动态骨组织形态计量学数据升高导致理想的骨平衡和骨强度。所获得的结果支持我们的理论，即抑制17 β-HSD 2型导致局部高雌激素和/或睾酮水平，从而维持骨形成和骨强度。总的来说，我们的数据表明，可以实现利用组织选择性和受体生物利用度将非活性激素转化为活性形式的治疗模式，并对靶组织（如骨骼和肌肉）产生理想的效果。
In both sexes, a reduction in sex steroid production with aging impairs the musculoskeletal system. The goal of our study was to test the ability of WH-9062, a novel non-steroidal small molecule inhibitor of the 17beta-Hydroxysteroid Dehydrogenase type 2 enzyme, to maintain or improve bone strength without raising serum levels of testosterone or estradiol. Mature, female cynomolgus monkeys with sealed growth plates were allocated into six groups: Sham controls, OVX controls, OVX+Premarin (15 mg/kg/d), and three groups of OVX monkeys receiving WH-9062 at 1, 5 and 25 mg/kg/day. All treatments were administered by daily oral dosing for 23 weeks. Changes in lipid profile caused by OVX were corrected with WH-9062 and included lowering total of cholesterol and non-HDL cholesterol, and maintenance of initial plasma levels of HDL cholesterol. Only the highest dose of WH-9062 lowered bone resorption relative to OVX controls. Elevated bone specific alkaline phosphatase, osteocalcin, BMC and dynamic bone histomorphometry data resulted in desirable bone balance and bone strength. The obtained results support our theory that inhibition of 17beta-HSD type 2 resulted in high local estrogen and/or testosterone levels leading to maintenance of bone formation and bone strength. Collectively, our data demonstrated that the treatment paradigm that utilizes tissue selectivity and receptor bioavailability in conversion of inactive hormones to active forms could be achieved and could result in desirable effects on target tissues such as bone and muscles.
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影响因子：
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Longcope,C;Baker,RS;Hui,SL;JohnstonJr,CC
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发表时间：
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影响因子：
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