van Bezooijen R L, Que I, Ederveen A G, Kloosterboer H J, Papapoulos S E, Löwik C W
Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
J Endocrinol. 1998 Oct;159(1):27-34. doi: 10.1677/joe.0.1590027.
Nitric oxide (NO) is a mediator of bone metabolism and its production is under the control of gender hormones in several cell types or tissues. Changes in endogenous NO production, measured as plasma nitrate+nitrite levels, may therefore contribute to ovariectomy (OVX)-induced bone loss. We studied plasma nitrate+nitrite levels and trabecular bone mineral density (TBMD) 4 weeks after sham-operation or OVX in rats receiving various hormonal treatments. OVX decreased plasma nitrate+nitrite levels significantly and this was accompanied by a significant decrease in TBMD. Treatment with oral ethinyl oestradiol (EE) and subcutaneous 17beta-oestradiol dose-dependently prevented the decrease in plasma nitrate+nitrite levels after OVX, but treatment with oral 17beta-oestradiol did not. Oestrogen treatment, 17beta-oestradiol (s. c. or orally) or EE (orally), prevented the OVX-induced decrease in TBMD. Treatment of sham-operated rats with the anti-oestrogen ICI164, 384 induced a significant decrease in TBMD that corresponded to 54% of the decrease observed after OVX, but did not affect plasma nitrate+nitrite levels. Treatment of ovariectomized rats with Org 2058, a pure progestagen, did not prevent bone loss, but prevented the decrease in plasma nitrate+nitrite levels dose-dependently. Treatment with tibolone, a synthetic steroid with combined weak oestrogenic, progestagenic, and androgenic properties, or with progestagen in combination with EE completely prevented bone loss after OVX. These treatments, however, only partly prevented the OVX-induced decrease in plasma nitrate+nitrite levels. In conclusion, OVX decreased both TBMD and plasma nitrate+nitrite levels. Although plasma nitrate+nitrite levels were under the control of both oestrogen and progesterone, TBMD was affected by oestrogen only. Decreased systemic production of NO is, therefore, not involved in OVX-induced bone loss in rats.
一氧化氮（NO）是骨代谢的介质，其生成在多种细胞类型或组织中受性激素调控。因此，以内源性NO生成变化（以血浆硝酸盐+亚硝酸盐水平衡量）可能导致卵巢切除（OVX）引起的骨质流失。我们研究了接受各种激素治疗的大鼠在假手术或OVX后4周时的血浆硝酸盐+亚硝酸盐水平和小梁骨矿物质密度（TBMD）。OVX显著降低了血浆硝酸盐+亚硝酸盐水平，同时伴有TBMD的显著降低。口服炔雌醇（EE）和皮下注射17β-雌二醇剂量依赖性地预防了OVX后血浆硝酸盐+亚硝酸盐水平的降低，但口服17β-雌二醇治疗则无此效果。雌激素治疗，即17β-雌二醇（皮下或口服）或EE（口服），预防了OVX引起的TBMD降低。用抗雌激素ICI164、384处理假手术大鼠，导致TBMD显著降低，相当于OVX后观察到的降低幅度的54%，但不影响血浆硝酸盐+亚硝酸盐水平。用纯孕激素Org 2058处理去卵巢大鼠，不能预防骨质流失，但剂量依赖性地预防了血浆硝酸盐+亚硝酸盐水平的降低。用替勃龙（一种具有弱雌激素、孕激素和雄激素特性的合成类固醇）或孕激素与EE联合治疗完全预防了OVX后的骨质流失。然而，这些治疗仅部分预防了OVX引起的血浆硝酸盐+亚硝酸盐水平降低。总之，OVX降低了TBMD和血浆硝酸盐+亚硝酸盐水平。虽然血浆硝酸盐+亚硝酸盐水平受雌激素和孕激素两者调控，但TBMD仅受雌激素影响。因此，全身NO生成减少与大鼠OVX诱导的骨质流失无关。
