Division of Endocrinology and Metabolism, Department of Medicine University Hospital, (CHUV) CH - 1011 Lausanne, Switzerland
Because of the well-known role of the thymus in the regulation
of immune function, we investigated whether the lack of thymus
may affect hypothalamo-pituitary-adrenal (HPA) axis activity.
Eight-week-old female Swiss nude (athymic) and BALB/c (normal)
mice were used to study (a) the "
in vivo" response of the HPA
axis to various stresses and stimuli acting at either hypothalamic,
pituitary, or adrenal levels and (b) the
in vitro response of
pituitary and adrenal cells to CRH and ACTH stimulation, respectively.
The results indicate that (1) basal plasma ACTH levels were
significantly (
p < 0.05) higher in Swiss nude than in BALB/c
mice, whereas basal corticosterone (B) levels were similar in
both strains of mice; (2) the stress-induced release of ACTH
and B in plasma was significantly (
p < 0.05) lower in Swiss
nude than in BALB/c mice, regardless of the stimulus applied;
(3) the "
in vitro" pituitary response to CRH and the adrenal
response to ACTH were significantly (
p < 0.05) lower in Swiss
nude than in BALB/c mice; and (4) whereas hypothalamic CRH and
pituitary ACTH contents were similar in both strains, adrenal
B content was significantly (
p < 0.05) lower in athymic mice.
Immune reconstitution of the athymic nude mice by injecting
splenocytes obtained from syngeneic heterozygous (i.e., immunologically
fully competent) donors produced a significant increase in the
B adrenal content of the nude mice. Among the splenocytes, CD4+
T-lymphocytes play a particularly important role in the release
of ACTH from cells of the immune system. In conclusion, our
results indicate that athymic nude mice have a blunted HPA axis
response to various stresses and stimuli; this defect seems
to reside at both the pituitary and adrenal levels. Immune reconstitution
of the nude mice leads to a normalization of the adrenal B content.
