CHRONIC MELATONIN TREATMENT AND THE HYPOTHALAMO-PITUITARY-ADRENAL AXIS IN THE RAT - ATTENUATION OF THE SECRETORY RESPONSE TO STRESS AND EFFECTS ON HYPOTHALAMIC NEUROPEPTIDE CONTENT AND RELEASE

The pituitary-adrenal secretory response to acute and chronic stress, suppressibility of adrenocortical secretions by exogenous glucocortico ids, and hypothalamic content and in vitro release of the two major pe ptidergic activators of the hypothalamo-pituitary-adrenal (HPA) axis, corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP), were examined in rats receiving daily melatonin (MEL) injections coinc ident with the circadian increment of endogenous pineal and adrenocort ical secretory activity. After 7 days of MEL administration, the rats displayed a significant attenuation of the adrenocortical secretory re sponse to acute and chronic stress. Chronic MEL treatment also prevent ed the decline in adrenocorticotropic hormone (ACTH) release resulting from chronic stress exposure. Hypothalamic CRH content was significan tly lower in rats receiving MEL treatment, while AVP remained largely unaltered; however, MEL administration counteracted the chronic stress -induced decrease in hypothalamic AVP content and in vitro release. Wh en exposed to dexamethasone in vitro, hypothalamic explants from MEL-t reated rats responded with a stronger suppression of CRH and AVP relea se than those originating from vehicle-injected animals. These observa tions indicate that MEL attenuates the adrenocortical response to stre ss and influences the biosynthesis, release and glucocorticoid respons iveness of hypothalamic ACTH secretagogues. ((C) Elsevier, Paris).