Institute of Social and Preventive Medicine, University of Lausanne, Lausanne, Switzerland.
Federal Food Safety and Veterinary Office, Risk Assessment Division, Bern, Switzerland.
J Clin Endocrinol Metab. 2018 Feb 1;103(2):748-758. doi: 10.1210/jc.2017-01540.
Urinary cadmium (Cd) excretion is associated with cancer and cardiovascular morbidity. A potential mechanism could be disturbance of steroidogenesis in gonads and adrenal glands.
We tested whether urinary excretion of Cd is correlated with that of cortico- and sex steroid metabolites in the general adult population.
The Swiss Kidney Project on Genes in Hypertension is a multicentric, family-based population study.
Urinary excretions of steroid hormone metabolites and Cd were measured with separate day and night collections. Associations were analyzed by mixed linear models.
Urinary Cd and testosterone excretions in men were significantly correlated (respective day and night β values [standard error (SE)], 1.378 [0.242], P < 0.0005; and 1.440 [0.333], P < 0.0005), but not in women [0.333(0.257), P = 0.2; and 0.674 (0.361), P = 0.06]. Urinary Cd and cortisol excretions were positively associated in both sexes [day: β = 0.475 (SE, 0.157), P = 0.0025, and 0.877 (SE, 0.194), P < 0.0005, respectively; night: β = 0.875 (SE, 0.253), P < 0.0005 and 1.183 (SE, 0.277), P = 0.00002, respectively]. Cd excretion was correlated with mineralocorticoid metabolites excretion, except tetrahydroaldosterone, in both sexes (P < 0.01). There was an independent effect of Cd on sex hormone and corticosteroid synthesis and an interdependent effect on gluco- and mineralcorticoid production.
Our findings provide evidence for a global stimulating effect on steroid synthesis already at low-dose Cd exposure. These findings might explain the association of Cd with diseases such as steroid-sensitive cancers or metabolic disorders.
尿镉（Cd）排泄与癌症和心血管发病率有关。潜在的机制可能是性腺和肾上腺甾体生成紊乱。
我们检测了普通成年人群中尿镉排泄是否与皮质类固醇和性激素代谢物有关。
瑞士高血压基因项目是一项多中心、基于家庭的人群研究。
分别进行了 24 小时和 12 小时的尿液收集，以检测类固醇激素代谢物和 Cd 的排泄。采用混合线性模型分析相关性。
男性的尿 Cd 和睾酮排泄呈显著正相关（相应的日和夜β值[标准误差（SE）]分别为 1.378[0.242]，P<0.0005；和 1.440[0.333]，P<0.0005），但女性则无相关性[0.333（0.257），P=0.2；和 0.674（0.361），P=0.06]。两性的尿 Cd 和皮质醇排泄呈正相关[日间：β=0.475（SE，0.157），P=0.0025；和 0.877（SE，0.194），P<0.0005]；夜间：β=0.875（SE，0.253），P<0.0005；和 1.183（SE，0.277），P=0.00002]。除四氢醛固酮外，两性的尿 Cd 排泄与盐皮质激素代谢物排泄呈负相关（P<0.01）。Cd 对性激素和皮质类固醇的合成有独立影响，对糖和盐皮质激素的产生有相互影响。
我们的研究结果为低剂量 Cd 暴露时甾体合成的整体刺激作用提供了证据。这些发现可能解释了 Cd 与类固醇敏感性癌症或代谢紊乱等疾病的关联。
