Glucocorticoid withdrawal affects stress-induced changes in urocortin 2 gene expression in the rat adrenal medulla and brain

Corticotrophin-releasing factor is a well known activator of the hypothalamic-pituitary-adrenocortical axis, which represents a crucial system participating in the stress response of an organism. Urocortins are members of the corticotrophin-releasing factor family of peptides with proposed effects on neuroendocrine and behavioural stress response mechanisms. Urocortin 2, which is one of three known urocortins, is present in the central and peripheral stress response system and its expression can be augmented by glucocorticoids. In the present study we examined how glucocorticoid withdrawal affects urocortin 2 gene expression after acute im-mobilisation in the adrenal medulla and selected brain areas in rats. We used pharmacological adrenalectomy to block the synthesis of corticosterone. The results obtained show that the immobilisation-induced rise in urocortin 2 mRNA levels in the rat adrenal medulla was not inhibited by glucocorticoid withdrawal. By contrast, observed changes in the brain indicate that the effect of stress and pharmacological adrenalectomy on urocortin 2 gene expression is site-specific. In the paraventricular nucleus and locus coeruleus, the immobilisation-induced rise of urocortin 2 was not inhibited by pharmacological adrenalectomy, whereas it was in the arcuate nucleus and central amygdala. Moreover, we have seen a significant depletion of urocortin 2 plasma levels after immobilisation. The immobilisation induced a rise of urocortin 2 gene expression in the rat adrenal medulla and brain areas regulating stress response pathways and the preservation of its induction after adrenalectomy suggests a role for urocortin 2 in the neuroendocrine stress response of an organism.