Minireview: Hair Cortisol: A Novel Biomarker of Hypothalamic-Pituitary-Adrenocortical Activity

Abstract

Activity of the hypothalamic-pituitary-adrenocortical (HPA) axis is commonly assessed by measuring glucocorticoids such as cortisol (CORT). For many years, CORT was obtained primarily from blood plasma or urine, whereas later approaches added saliva and feces for noninvasive monitoring of HPA functioning. Despite the value of all these sample matrices for answering many research questions, they remain limited in the temporal range of assessment. Plasma and saliva are point samples that vary as a function of circadian rhythmicity and are susceptible to confounding by environmental disturbances. Even urine and feces generally assess HPA activity over a period of only 24 h or less. We and others have recently developed and validated methods for measuring the concentration of CORT in the body hair of animals (e.g. rhesus monkeys) and scalp hair of humans. CORT is constantly deposited in the growing hair shaft, as a consequence of which such deposition can serve as a biomarker of integrated HPA activity over weeks and months instead of minutes or hours. Since the advent of this methodological advance, hair CORT has already been used as an index of chronic HPA activity and stress in human clinical and nonclinical populations, in a variety of laboratory-housed and wild-living animal species, and in archival specimens that are many decades or even centuries old. Moreover, because human hair is known to grow at an average rate of about 1 cm/month, several studies suggest that CORT levels in hair segments that differ in proximity to the scalp can, under certain conditions, be used as a retrospective calendar of HPA activity during specific time periods preceding sample collection.

Extraction and Analysis of Cortisol from Human and Monkey Hair

“…Second, whereas the use of hair CORT will likely be of particular value to researchers interested in psychosocial and environmental stressors, it is important to keep in mind that elevated HPA activity can occur under a variety of conditions, including physical exercise, metabolic abnormalities, and infectious disease. Third, whereas data exist from both humans and monkeys supporting the hypothesis that hair CORT is derived mainly from the bloodstream 2 , this hypothesis has not yet been proven. Indeed, Ito and coworkers 16 have demonstrated the existence of a functional HPA-like system in microdissected human hair follicles maintained in organ culture.…”

“…Measuring CORT in hair rather than plasma or saliva offers a number of advantages 2 . Most importantly, this approach provides a biomarker of integrated CORT levels over periods of weeks to months that is uninfluenced by the time of day when samples are collected or by brief stress exposure prior to collection.…”

“…Place the hair sample in a pouch made of aluminum foil, a clean paper envelope, or a 15 ml screw-cap polypropylene centrifuge tube of the type used for sample washing. As CORT is extremely stable in hair 2 , samples can be stored indefinitely at -20 °C and, if necessary, shipped overnight at ambient temperature. 4.…”

“…Initial studies by several laboratories demonstrated the presence of CORT in human hair but did not investigate whether hair CORT levels changed as a function of stress 2 . As our laboratory has been interested for many years in the regulation of the rhesus monkey HPA axis by various social and behavioral factors 3 , we set out to establish and validate methods for extraction and analysis of rhesus monkey hair 4 .…”

“…First, previous studies had shown that small amounts of circulating CORT are excreted in sweat and sebum and therefore could coat the outside of the hair shaft 2 . In order to eliminate this potential confound, we developed a mild wash procedure that appears to remove external CORT while having a minimal effect on CORT present within the growing hair shaft.…”