Comparative effects of long-term continuous release of 16 alpha-hydroxyestrone and 17 beta-estradiol on bone, uterus, and serum cholesterol in ovariectomized adult rats.
Comparative effects of long-term continuous release of 16 alpha-hydroxyestrone and 17 beta-estradiol on bone, uterus, and serum cholesterol in ovariectomized adult rats.
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长期持续释放 16 α-羟基雌酮和 17 β-雌二醇对去卵巢成年大鼠骨、子宫和血清胆固醇的影响比较。
DOI：
10.1016/s8756-3282(03)00081-4
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发表时间：
2003
期刊：
影响因子：
4.1
通讯作者：
Turner,RussellT
中科院分区：
文献类型：
--
作者：
Lotinun,Sutada;Westerlind,KimC;Kennedy,AngelaM;Turner,RussellT
16α-羟基雌酮（16α-OHE 1）是一种内源性雌激素代谢产物，与绝经后妇女骨密度增加相关。本研究旨在评价该代谢物对绝经后骨丢失动物模型中骨、子宫和血清胆固醇的长期活性。在断奶大鼠中进行的初步剂量-反应研究确定2000 μg/kg/天是研究雌激素对骨作用的16α-OHE 1的最佳剂量。在6个月大的动物中进行长期实验，这些动物要么是假手术要么是OVX。去卵巢大鼠皮下植入17β-雌二醇（E2）缓释载体（33 μg/kg/d）或16α-OHE 11缓释微丸（2000 μg/kg/d），持续60 d。OVX降低了子宫重量，增加了体重，血清胆固醇和皮质骨和松质骨的所有动态骨组织形态测量值，并导致胫骨干骺端54%的骨丢失。E2完全阻止了OVX诱导的骨丢失，抑制骨转换，并诱导子宫肥大和高胆固醇血症。16α-OHE 1作为E2激动剂作用于骨，抑制骨形成和骨吸收。然而，雌激素代谢产物降低了血清胆固醇，并且仅是子宫重量和上皮细胞高度的部分E2激动剂。这些结果表明，16α-OHE 1是骨上的雌激素激动剂，并且可能部分负责归因于雌激素的降胆固醇活性。由于其对骨骼的影响，产生高水平16α-OHE 1的老年女性发生绝经后骨质疏松症的风险可能低于产生较低活性雌激素代谢产物的女性。
16α-Hydroxyestrone (16α-OHE1), an endogenous estrogen metabolite, is associated with increased bone density in postmenopausal women. This study was designed to evaluate the long-term activity of this metabolite on bone, uterus, and serum cholesterol in an animal model for postmenopausal bone loss. A preliminary dose–response study performed in weanling rats determined 2000 μg/kg/day to be the optimal dose of 16α-OHE1for studying estrogenic effect on bone. The long-term experiment was performed in 6-month-old animals that were either sham-operated or OVX. The OVX rats were implanted sc with 60-day continuous-release carrier, 17β-estradiol (E2) (33 μg/kg/day) or 16α-OHE1pellets (2000 μg/kg/day). OVX decreased uterine weight, increased body weight, serum cholesterol, and all dynamic bone histomorphometric measurements in cortical and cancellous bone, and resulted in a 54% bone loss at the tibial metaphysis. E2completely prevented OVX-induced bone loss, suppressed bone turnover, and induced uterine hypertrophy and hypercholesterolemia. 16α-OHE1acted as an E2agonist on bone, suppressing bone formation and resorption. However, the estrogen metabolite lowered serum cholesterol and was only a partial E2agonist on uterine weight and epithelial cell height. These results suggest that 16α-OHE1is an estrogen agonist on bone and may be responsible, in part, for the cholesterol-lowering activity attributed to estrogen. As a consequence of its skeletal effects, older women who produce high levels of 16α-OHE1could have a lower risk for developing postmenopausal osteoporosis than women who produce less-active estrogen metabolites.