TY - JOUR

T1 - Hair glucocorticoids are not a historical marker of stress

T2 - Exploring the time-scale of corticosterone incorporation into hairs in a rat model

AU - Colding-Jørgensen, Pernille

AU - Hestehave, Sara

AU - Abelson, Klas S.P.

AU - Kalliokoski, Otto

N1 - Funding Information: This study was in part funded by the Center for Applied Laboratory Animal Research (CALAR) and the purchase of laboratory equipment was made possible through Brødrena Hartmanns Fond. The financers had no part in designing/interpreting the study and the authors have no conflicts of interest to report. Publisher Copyright: © 2023 The Author(s)

PY - 2023

Y1 - 2023

N2 - Hair glucocorticoids are increasingly popular biomarkers, used across numerous research fields, and studied species, as a measure of stress. Although they are suggested to be a proxy of the average HPA axis activity spanning a period of weeks or months into the past, this theory has never been tested. In the present study, adrenalectomized rats with no endogenous (adrenal) glucocorticoid production were used to study how circulating glucocorticoid levels would be reflected in the glucocorticoid levels found in hair samples. By dosing the animals daily with high levels of corticosterone for seven days, while sampling hairs before, during, and after treatments, a timeline for glucocorticoid uptake into hairs was constructed. This kinetic profile was compared to two hypothetical models, and the theory that hair glucocorticoids are a record of historical stress had to be rejected. Corticosterone concentrations in hairs were found to increase within three hours of the first injection, the highest concentrations were found on the seventh day of treatments, and the decrease in concentrations post-treatment suggests rapid elimination. We speculate that hair glucocorticoid levels can only be used to characterize a stress-response for a few days following a postulated stressor. An updated model, where glucocorticoids diffuse into, along, and out of hairs needs to be adopted to reconcile the experimentally obtained data. The inescapable consequence of this updated model is that hair glucocorticoids become a marker of – and can only be used to study – recent, or ongoing, stress, as opposed to historical events, weeks or months in the past.

AB - Hair glucocorticoids are increasingly popular biomarkers, used across numerous research fields, and studied species, as a measure of stress. Although they are suggested to be a proxy of the average HPA axis activity spanning a period of weeks or months into the past, this theory has never been tested. In the present study, adrenalectomized rats with no endogenous (adrenal) glucocorticoid production were used to study how circulating glucocorticoid levels would be reflected in the glucocorticoid levels found in hair samples. By dosing the animals daily with high levels of corticosterone for seven days, while sampling hairs before, during, and after treatments, a timeline for glucocorticoid uptake into hairs was constructed. This kinetic profile was compared to two hypothetical models, and the theory that hair glucocorticoids are a record of historical stress had to be rejected. Corticosterone concentrations in hairs were found to increase within three hours of the first injection, the highest concentrations were found on the seventh day of treatments, and the decrease in concentrations post-treatment suggests rapid elimination. We speculate that hair glucocorticoid levels can only be used to characterize a stress-response for a few days following a postulated stressor. An updated model, where glucocorticoids diffuse into, along, and out of hairs needs to be adopted to reconcile the experimentally obtained data. The inescapable consequence of this updated model is that hair glucocorticoids become a marker of – and can only be used to study – recent, or ongoing, stress, as opposed to historical events, weeks or months in the past.

U2 - 10.1016/j.ygcen.2023.114335

DO - 10.1016/j.ygcen.2023.114335

M3 - Journal article

C2 - 37302763

AN - SCOPUS:85164531867

VL - 341

JO - General and Comparative Endocrinology

JF - General and Comparative Endocrinology

SN - 0016-6480

M1 - 114335

ER -