Individual differences in adrenal axis activity and stress sensitivity in female cynomolgus monkeys (Macaca fascicularis)

Stress‑induced amenorrhea in women is thought to result from heightened sensitivity to everyday psychosocial and metabolic stress, which suppresses GnRH drive and disrupts reproductive function. Using a nonhuman primate model, this dissertation examined neural mechanisms underlying stress‑related reproductive dysfunction. Female cynomolgus monkeys exposed to mild combined stress were categorized by stress sensitivity. Stress‑sensitive animals showed increased daytime cortisol only during combined stress, but baseline HPA activity did not differ across groups. Pharmacological blockade of CRH‑R1 prevented stress‑induced suppression of LH pulses, indicating CRH acts through pathways outside the HPA axis. Immunocytochemistry revealed greater CRH input to serotonin‑producing raphe nuclei in stress‑sensitive monkeys. These findings suggest interactions between CRH and serotonin systems contribute to stress‑induced reproductive suppression and highlight new directions for understanding the etiology of stress‑related amenorrhea.