R. Konakchieva et al., CHRONIC MELATONIN TREATMENT COUNTERACTS GLUCOCORTICOID-INDUCED DYSREGULATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN THE RAT, Neuroendocrinology, 67(3), 1998, pp. 171-180
Transient exposure of rats to high doses of dexamethasone (DEX; 500 mu
g/day for 5 days) produced a host of symptoms that are indicative of
hypothalamic-pituitary-adrenal (HPA) axis dysregulation, such as incre
ased adrenocortical secretion over 24 h, blunted and prolonged secreto
ry,response to emotional stress, refractoriness of adrenocorticotropin
in vitro release to stimulation with the secretagogues corticotropin-
releasing hormone (CRH) and vasopressin, decreased levels of mRNA enco
ding type II corticosteroid receptors in the hippocampus and increased
numbers of transcripts encoding CRH in the paraventricular nucleus. D
aily administration of melatonin (MEL; 80 mu g/kg) concomitantly with,
and for 5 days after discontinuation of, glucocorticoid treatment 'no
rmalized' most of the symptoms of impaired HPA regulation caused by th
e exposure to DEX, While none of the treatments used caused major shif
ts in circadian patterns of corticosterone secretion, MEL administrati
on was associated with diminished overall corticosterone secretion and
increased sensitivity to glucocorticoid feedback. Taken together, the
se findings indicate that chronic MEL treatment may protect several re
gulatory components of the HPA axis from glucocorticoid-induced deteri
oration.