Gaumet N, Seibel M J, Coxam V, Davicco M J, Lebecque P, Barlet J P
Centre de Recherche Clermont-Theix, Ceyrat, France.
Arch Physiol Biochem. 1997 Sep;105(5):435-44. doi: 10.1076/apab.105.5.435.3292.
Study was carried out an Wistar female rats to evaluate the consequences of ovariectomy and 17 beta-estradiol substitutive treatment during aging on bone. Ca metabolism and calciotropic hormones. Three groups of fifteen rats, mature, old and senescent (4-, 10-, and 28 month-old) female were fed a diet (6 g/100 g BW/day) containing 0.9% Ca and 0.8% Pi, Within each group, 10 rats were surgically ovariectomized (OVX). From day 1 until day 60 after OVX, they were subcutaneously injected with either 17 beta-estradiol (E: 10 micrograms/kg BW/48 h; n = 5) or with solvent alone (OVX; n = 5). Five other rats were sham operated (SH) and received solvent alone. Animals were put in balance 1 day per week to determine Ca and Pi intestinal apparent absorption and urinary pyridinium cross-links excretion was measured by HPLC. All rats were killed by exsanguination 60 days after OVX. Plasma was collected for measurement of intact parathyroid hormone (PTH), calcitonin (CT), insulin-like growth factor-1 (IGF-1), Ca and Pi. The success of OVX was confirmed at necropsy by observation of marked atrophy of the uterine horns. The right femur was collected, cleaned from adjacent tissue and used for mineral analysis. Despite correct matching for feeding, BW was significantly larger in 6 and 12 month-old OVX rats. OVX and 17 beta-estradiol had no significant effect upon plasma Ca, Pi and CT concentrations. Aging is associated with increased circulating PTH levels (pg/ml) (SH-6 months: 50.8 +/- 12.6; 12 months: 219.1 +/- 34.9; 30 months: 158.7 +/- 23.5; P < 0.05). Urinary and fecal Ca and Pi excretion in senescent animals were higher than in adult or old rats, thus resulting in a drastic fall in both intestinal apparent absorption and retention of Ca and Pi in 30 month-old animals. In each group, urinary pyridinium cross-links excretion and plasma osteocalcin concentration were higher in the OVX animals than in the controls, consistent with increased bone turnover in the estrogen deficient state. Both biochemical turnover markers were reduced in the estrogen-treated groups. In the same way, OVX increased and estrogen decreased the plasma IGF-1 levels. We conclude that 17 beta-estradiol prevents high turnover-induced osteopenia even in 30 month-old rats.
对雌性Wistar大鼠进行研究,以评估衰老过程中卵巢切除术及17β-雌二醇替代治疗对骨骼、钙代谢和钙调节激素的影响。将三组各15只大鼠,即成熟、老龄和衰老(4、10和28月龄)雌性大鼠,饲喂含0.9%钙和0.8%磷的日粮(6 g/100 g体重/天)。每组中,10只大鼠接受手术卵巢切除(OVX)。在OVX后第1天至第60天,它们皮下注射17β-雌二醇(E:10微克/千克体重/48小时;n = 5)或仅注射溶剂(OVX;n = 5)。另外5只大鼠接受假手术(SH)并仅接受溶剂。每周将动物置于天平上称重1天,以测定钙和磷的肠道表观吸收,并通过高效液相色谱法测量尿吡啶交联物排泄。OVX后60天,所有大鼠通过放血处死。收集血浆以测量完整甲状旁腺激素(PTH)、降钙素(CT)、胰岛素样生长因子-1(IGF-1)、钙和磷。尸检时通过观察子宫角明显萎缩证实OVX成功。收集右股骨,清除相邻组织并用于矿物质分析。尽管在喂养方面进行了正确匹配,但6月龄和12月龄OVX大鼠的体重显著更大。OVX和17β-雌二醇对血浆钙、磷和CT浓度无显著影响。衰老与循环PTH水平升高相关(pg/ml)(SH-6月龄:50.8±12.6;12月龄:219.1±34.9;30月龄:158.7±23.5;P<0.05)。衰老动物的尿和粪便钙及磷排泄高于成年或老龄大鼠,因此30月龄动物的肠道表观吸收以及钙和磷的潴留均急剧下降。每组中,OVX动物的尿吡啶交联物排泄和血浆骨钙素浓度均高于对照组,这与雌激素缺乏状态下骨转换增加一致。雌激素治疗组的两种生化转换标志物均降低。同样,OVX使血浆IGF-1水平升高,而雌激素使其降低。我们得出结论,即使在30月龄大鼠中,17β-雌二醇也能预防高转换诱导的骨质减少。