IMPAIRED HYPOTHALAMO-PITUITARY-ADRENAL AXIS FUNCTION IN SWISS NUDE ATHYMIC MICE

Various evidence suggests a bidirectional circuit between the immune a nd neuroendocrine systems. Because of the well-known role of the thymu s in the regulation of the immune function, we designed this study to determine whether the lack of thymus may affect hypothalamo-pituitary- adrenal (HPA) axis activity by using both in vivo and in vitro paradig ms in Swiss nude (athymic) and BALB/c (normal) mice. Eight-week-old fe male mice of both strains were used to study: (a) the in vivo response of the HPA axis to various stress stimuli acting at either hypothalam ic (ether vapor inhalation, insulin administration), pituitary (CRH in jection) or adrenal (ACTH treatment) level and (b) the in vitro respon se of pituitary and adrenal cells to CRH and ACTH stimulation, respect ively. The results indicate that: (1) basal plasma ACTH levels were si gnificantly (p < 0.05) higher in Swiss nude than in BALB/c mice, where as basal plasma corticosterone (B) concentrations were similar in both strains of mice; (2) the stress-induced release of ACTH and B in plas ma were significantly (p < 0.05) lower in Swiss nude than in BALB/c mi ce, regardless of the stimulus applied; (3) the in vitro pituitary res ponse to CRH and the adrenal response to ACTH were significantly (p < 0.05) lower in Swiss nude than in BALB/c mice, whereas (4) hypothalami c CRH and pituitary ACTH contents were similar in both strains, adrena l B concentration was significantly (p < 0.05) lower in athymic mice; in addition, the nude mice adrenal glands were larger than those of BA LB/c animals, due to marked hypertrophy of the zona fasciculata. In co nclusion, our results indicate that athymic nude mice have a blunted H PA axis response to various stress stimuli; this defect seems to resid e at both the pituitary and adrenal levels. It remains to be determine d whether this impairment is directly related to the immunodeficiency of this animal model.