Responses of the porcine pituitary-adrenal axis to chronic intermittent stressor

Abstract

Initial responses and adaptation of the porcine pituitary-adrenal axis to a chronic intermittent stressor (45-min daily restraint for 8 or 9 d) and effects of this stressor on binding to adrenocortical ACTH receptors were measured. Blood samples were obtained via indwelling jugular catheters on days 1, 5, and 9. On day 9, barrows (castrated male pigs; 40 kg) were killed and adrenal glands obtained. Binding to adrenal ACTH receptors was measured using [ 125I]Tyr 23,Phe 2,Nle 4ACTH(1–38) analog. Basal (prestressor) ACTH, cortisol, and PRL concentrations were not affected by 9 d of 45-min restraint daily (RES-9). In RES-9 barrows, integrated ACTH responses to restraint decreased 46% (P<.05) between day 1 and day 5, then remained constant through day 9. Integrated PRL and cortisol responses were 28 to 30% lower on day 9 than on day 1 (P<05). On day 9 integrated ACTH responses for RES-9 pigs were 59% lower than those of pigs exposed to a single 45-min restraint on day 9 (P<.05), whereas integrated cortisol responses were similar. Responsiveness of the pituitary-adrenal axis on day 9, 24 hr after the last of 8 daily 45-min restraints (RES-8), was compared with that of previously unstressed (naive) pigs. Exposure of RES-8 and naive pigs to a novel stressor (i.m. saline injection) produced plasma ACTH and cortisol responses of comparable magnitude. Intravenous injection of 2 μg ACTH (1–24) to RES-8 and naive pigs produced plasma cortisol responses of comparable magnitude. Plasma ACTH responses were 49% less (P<.05) in RES-8 pigs, and were associated with 65% increases (P=.02) of ACTH apparent metabolic clerance rates (ml/min/kg body weight), and 49% increases (P=.06) in ACTH apparent volumes of distribution (ml/kg body weight). In RES-8 pigs vs naive pigs, the ratio of integrated cortisol/integrated plasma ACTH was greater (P<.01) after ACTH injection, and the plasma cortisol response occurred more rapidly. Thus, RES-8 pigs appeared to be more responsive to ACTH. Since binding of ACTH to adrenocortical receptors did not differ between RES-8 or RES-9 pigs and controls, changes in ACTH receptors cannot account for differences in responsiveness. These data indicate chronic intermittent stressor-associated changes occur in functioning of the porcine pituitary-adrenal axis which are not apparent when considering only basal hormonal concentrations.