Effects of the estrous cycle and sex on stress responses in guinea pigs

Sex differences in hypothalamic-pituitary-adrenal (HPA)-axis functions and related stress responsiveness can strongly depend on influences of gonadal hormones and their fluctuations during the female estrous or menstrual cycle. Females usually show higher HPA-axis activity and glucocorticoid concentrations in the preovulatory phases of the cycle than in the other phases and compared to males. The guinea pig represents a potential model species in this context, but little and inconclusive information on sex differences and estrous cycle effects on HPA-axis activity is available in this species. This study investigated basal saliva cortisol concentrations and stress responses to a 1-h social separation stressor in an open-field-like novel environment in female (n = 16) and male (n = 16) guinea pigs aged 0.5-2.5 years. All guinea pigs were sampled and tested repeatedly: females during diestrus and estrus of two estrous cycles, and males twice at comparable intervals. Basal cortisol concentrations were significantly increased in females during estrus compared to diestrus and males. Cortisol concentrations increased strongest in response to the stress test in females during diestrus and the smallest increase was found during estrus. This resulted in significantly higher cortisol concentrations after the test in females during diestrus compared to males. The results were highly robust with regard to repeated testing and individual age. The estrous cycle of female guinea pigs clearly contributes to sex differences in cortisol concentrations and stress responses, which strongly calls for consideration of both in future investigations.