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肥胖绝经后女性游离睾酮的昼夜浓度、骨代谢的选定标志物、骨保护素及其配体sRANKL

Circadian concentrations of free testosterone, selected markers of bone metabolism, osteoprotegerin and its ligand sRANKL in obese postmenopausal women.

作者信息

Ostrowska Zofia, Kos-Kudła Beata, Marek Bogdan, Kajdaniuk Dariusz, Wołkowska-Pokrywa Kinga

机构信息

Clinical Biochemistry Division, Department of Biochemistry, Medical University of Silesia, Zabrze, Poland.

出版信息

Postepy Hig Med Dosw (Online). 2011 Oct 11;65:658-67. doi: 10.5604/17322693.962637.

DOI:10.5604/17322693.962637
PMID:22100799
Abstract

BACKGROUND

It has been suggested that increased testosterone secretion in postmenopausal obese women might have some protective effect on bone tissue; the association might be significantly influenced by the RANKL/RANK/OPG system.

AIM

The aim of the study was to determine whether postmenopausal obese women showed any relationship between the pattern of adipose tissue distribution, circadian free testosterone (FT) concentrations and bone metabolism (as assessed based on circadian osteocalcin [OC] and C-terminal telopeptide [CTx] levels), and to establish whether osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) might play a role in the relationship.

MATERIAL/METHODS: FT, OC, CTx, OPG and soluble RANKL (sRANKL) levels were determined by ELISA in serum samples collected every three hours for 24 hours from 47 postmenopausal women (12 with gynoid obesity [GO], 17 with android obesity [AO], and 18 healthy individuals).

RESULTS

Obese women demonstrated an adipose tissue distribution-dependent increase in mean circadian FT levels and a decrease in mean circadian OC, CTx, OPG and sRANKL compared to control participants. In GO subjects, these changes were accompanied by smaller FT amplitudes, suppression of the circadian rhythms of bone markers and OPG, and a shift of sRANKL rhythm acrophase, whereas AO subjects showed a decrease in bone marker amplitudes and suppression of OPG and sRANKL rhythms. In comparison with the controls, significant adipose tissue distribution-dependent changes were found in the correlations between FT and bone markers, FT and OPG, OC and CTx, OPG and sRANKL, CTx and OPG, and CTx and sRANKL. Compared to GO participants, those with AO had higher coefficients of correlations between mean circadian FT and OC as well as between OC and CTx, and lower in the case of FT and sRANKL as well as CTx and OPG and CTx and sRANKL.

DISCUSSION/CONCLUSIONS: Postmenopausal obesity results in adipose tissue distribution-dependent alterations in circadian FT levels accompanied by suppression of bone metabolism and a decline in circadian variations of the osteokines under investigation, especially sRANKL. Increased FT secretion in postmenopausal women might exert a protective effect on bone tissue, most likely via a shift in the OPG/RANKL ratio that tilts the balance toward a functional excess of OPG.

摘要

背景

有人提出,绝经后肥胖女性睾酮分泌增加可能对骨组织有一定保护作用;这种关联可能受RANKL/RANK/OPG系统的显著影响。

目的

本研究旨在确定绝经后肥胖女性的脂肪组织分布模式、昼夜游离睾酮(FT)浓度与骨代谢(根据昼夜骨钙素[OC]和C端肽[CTx]水平评估)之间是否存在任何关系,并确定骨保护素(OPG)和核因子κB受体激活剂配体(RANKL)是否在这种关系中起作用。

材料/方法:通过酶联免疫吸附测定法(ELISA)测定47名绝经后女性(12名臀部肥胖[GO]、17名腹部肥胖[AO]和18名健康个体)每3小时采集一次的血清样本中的FT、OC、CTx、OPG和可溶性RANKL(sRANKL)水平,共采集24小时。

结果

与对照组相比,肥胖女性的平均昼夜FT水平呈现出脂肪组织分布依赖性增加,而平均昼夜OC、CTx、OPG和sRANKL水平降低。在GO组中,这些变化伴随着较小的FT振幅、骨标志物和OPG昼夜节律的抑制以及sRANKL节律峰相位的偏移,而AO组则表现为骨标志物振幅降低以及OPG和sRANKL节律的抑制。与对照组相比,FT与骨标志物、FT与OPG、OC与CTx、OPG与sRANKL、CTx与OPG以及CTx与sRANKL之间的相关性存在显著的脂肪组织分布依赖性变化。与GO组参与者相比,AO组参与者的平均昼夜FT与OC之间以及OC与CTx之间的相关系数更高,而FT与sRANKL以及CTx与OPG和CTx与sRANKL之间的相关系数更低。

讨论/结论:绝经后肥胖导致昼夜FT水平出现脂肪组织分布依赖性改变,同时伴有骨代谢抑制以及所研究的骨因子(尤其是sRANKL)昼夜变化的下降。绝经后女性FT分泌增加可能对骨组织发挥保护作用,最有可能是通过OPG/RANKL比值的改变,使平衡向OPG功能过剩倾斜。

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