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Postnatal Glucocorticoids Affect Adaptation to Stress

Glucocorticoid receptors regulate hypothalamic-pituitary-adrenal axis activity

MONDAY, Feb. 23 (HealthDay News) -- Postnatal glucocorticoid excess due to deletion of pituitary glucocorticoid receptors affects the ability of adult mice to cope with stress, according to research published online Feb. 12 in Endocrinology.

To examine whether pituitary glucocorticoid receptors are involved in regulating the hypothalamic-pituitary-adrenal axis, which is important in adapting to stressful stimuli, Mathias V. Schmidt, Ph.D., from the Max Planck Institute of Psychiatry in Munich, Germany, and colleagues generated mice where pituitary glucocorticoid receptors could be specifically deleted.

The researchers found that the mice had higher postnatal basal corticosterone levels, accompanied by changes in the expression of corticotropin-releasing hormone and vasopressin in the paraventricular nucleus, but which normalized with age. As adults, the mice had impaired glucocorticoid negative feedback. Behaviorally, the adult mice showed a more active coping strategy in the forced swim test without changes in anxiety-like behavior or cognitive functions, the authors report. Postnatal treatment with a glucocorticoid receptor antagonist could prevent these long-term behavioral effects, according to the study.

"In conclusion, we show that pituitary glucocorticoid receptors are centrally involved in regulating hypothalamic-pituitary-adrenal axis activity in neonates and mediate negative feedback regulation in adult animals," Schmidt and colleagues write. "Postnatal glucocorticoid excess results in an altered stress-coping behavior in adult animals, with no effects on anxiety-like behavior or cognition."

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