Effects of chronic stress and gender on HPA axis responsivity in a pharmacologic CRH-AVP challenge test

Findings in rodents document an increased central AVP release after repeated stress suggesting that AVP may be the predominant ACTH secretagogue under chronic stress conditions. We intended to test whether this altered AVP regulation can be demonstrated via a pharmacological challenge in chronically stressed humans. Two groups of school teachers (21 men, 21 women) reporting either high or low levels of perceived chronic stress received a single injection of 50µg hCRH compared to the same injection during concomitant infusion of 100ng/min AVP. While the synergistic effect of the combined CRH-AVP application normally results in an augmented cortisol response compared to CRH alone, we postulated that higher pre-existing levels of central AVP in stressed subjects should result in a blunted response to the combined CRH-AVP injection compared to the non stressed group. The postulated attenuation of HPA responses to the CRH-AVP administration in stressed subjects was observed only as a marginally significant effect resp. at a trend level. However, these effects disappeared when gender was included as a covariate. A significant interaction gender x challenge test (p<.05 for salivary cortisol; p<.01 for plasma cortisol and ACTH) indicated a lower response to single CRH administration but higher responses to the combined CRH-AVP challenge in women compared to men. Also, CBG levels were significantly higher in women compared to men during both stimulation tests (p<.05). We speculate that the distinct impact of gender may have masked a possibly existing stress effect. Our results contribute further data to the ongoing discussion about the role of gonadal steroids and CBG on the HPA axis activity.