Increased lead biomarker levels are associated with changes in hormonal response to stress in occupationally exposed male participants

Abstract

Background: Lead (Pb) exposure has been associated with a host of pathological conditions in humans. In rodents Pb exposure has been shown to alter the hypothalamic-pituitary-adrenal (HPA) axis function.

Objective: We investigated the effects of lead on responses of the HPA axis to a psychosocial laboratory stressor administered to Pb-exposed workers.

Methods: Seventy male participants completed the Trier Social Stress Test (TSST). Serum cortisol (CORT) and plasma adrenocorticotropic hormone (ACTH) were assessed in response to and during recovery from the stressor. We measured Pb in blood, a biomarker of recent exposure, and in tibia bone by X-ray fluorescence (XRF), a biomarker of chronic exposure.

Results: The TSST induced statistically significant increases in ACTH and CORT in the participants. At baseline, ACTH was not significantly higher (p = 0.052) in participants with higher blood Pb concentration, but CORT was significantly lower in these participants (p = 0.016). Adjusted linear regression models indicated a positive association between blood and bone Pb and the increase in ACTH in response to stress. However, Pb was not strongly associated with changes in CORT in response to stress. Pb was also associated with the ACTH:CORT ratio at baseline and throughout the course of the protocol, suggesting an adrenal hyporesponsiveness in participants with higher Pb concentrations.

Conclusion: The altered HPA-axis stress response observed in participants exposed to higher levels of Pb further supports the idea that lead may contribute to a host of biological dysfunctions beyond the classical neurotoxic effects.

Figure 1

Protocol timeline. Blood was sampled 10 times during the protocol. Other questionnaires were self-administered at home before the laboratory session.

Figure 2

Time profile for the ACTH:CORT ratio (mean ± SE) in low (≤ 4 µg/dL) and high (> 4 µg/dL) BPb groups. The ACTH:CORT ratio illustrates the difference between these two components during the stress response in these two groups. An elevated ACTH:CORT ratio indicates a weaker adrenal responsivity to ACTH (Nater et al. 2010). The arrow indicates the execution of the TSST. *p < 0.05 for the analysis of covariance.