Temporal Changes in Plasma Adrenocorticotropin Concentration after Repeated Neurotropic Stress in Male and Female Rats

To test the ability of the pituitary gland to secrete ACTH in response to repeated stress, 90-day-old male and female rats were subjected first to a 3-min psychological stress and then to a second identical stress 5, 10, or 15 min after the onset of the first stress. After decapitation 5, 10, 15, 20, 25, or 35 min after the onset of the second stress, plasma ACTH concentration was determined by bioassay, and plasma corticosterone was measured by a fluorometric method. Although the rate of increase in plasma corticosterone levels after the first stress was about 1.4 μg/100 ml-min in males and 2.1 μg/100 ml-min in females, 5-15 min after the onset of the first stress, no rapid inhibition of the second stress response appeared. Gradual hypersecretion of ACTH occurred in males after exposure to the second stress, and the resultant peak increment in plasma ACTH concentration was 2–3 times greater than the one observed in once-stressed rats. In females, a rapid and significant increase in plasma ACTH concentration occurred, but the ratio was only 0.6:0.9 compared to the control group. These results suggest that the fast feedback inhibition mechanism by endogenous corticosterone is overcome by a more powerful facilitatory effect of the first stress on subsequent ACTH release and that these two antagonistic systems which regulate ACTH release in response to subsequent stress may be sex-related in their onset and magnitude.