Effects of cadmium and lead co-exposure on glucocorticoid levels in rural residents of northwest China

Cadmium (Cd) and lead (Pb) are important environmental endocrine disruptors that are associated with adverse health problems. However, the effects of co-exposure to Cd and Pb on glucocorticoids (GCs) in the body at environmental levels are limited. A total of 468 subjects from the Dongdagou-Xinglong cohort (DDG-XL) were included in this study. We measured the serum levels of two representative endogenous GCs [cortisol (CRL) and cortisone (CRN)], and whole blood levels of Cd and Pb. Multiple linear regression models were constructed to explore the associations of single or combined Cd and Pb exposure with serum CRL and CRN levels. The interactive effects of Cd and Pb on GCs were further assessed using mediation analysis and moderation analysis. Single-heavy metal exposure analysis with adjustment for potential confounders showed that the serum CRL level decreased when the blood Cd or Pb concentration gradually increased (P trend <0.01). Additionally, subjects with high Cd or Pb exposure (Q4) had significantly reduced serum CRN levels compared to those with low Cd or Pb exposure (Q1) (P < 0.05). In Cd and Pb co-exposure analysis, significant negative dose-response relationships were observed between co-exposure to Cd and Pb and serum CRL and CRN levels. Furthermore, mediation analysis showed that Cd completely mediated the relationship between Pb and GCs, and moderation analysis suggested that Pb might weaken the negative relationship between Cd and GCs. These findings suggest that single or combined exposure to Cd and Pb interferes with the homeostasis of serum CRL and CRN levels. Furthermore, we innovatively propose that Cd and Pb may have interactive effects on GCs levels, and Pb can antagonize the negative relationship between Cd and GCs, which may provide clues for further studies on endocrine and metabolic disorders related to these heavy metals.