Divergent effects of glucocorticoid on the gene expression of vasoactive intestinal peptide in the rat cerebral cortex and pituitary.

We investigated the effects of glucocorticoid on the expression of the vasoactive intestinal peptide (VIP) gene, a neuropeptide and an established prolactin (PRL)-releasing factor, in the rat brain and pituitary. The mRNA and peptide contents of VIP in the cerebral cortex, hypothalamus and anterior pituitary of male Sprague-Dawley rats were quantitated 4 weeks after adrenalectomy or sham-operation. Following adrenalectomy, VIP mRNA content increased in the anterior pituitary but showed no significant change in the cerebral cortex and hypothalamus. Dexamethasone treatment for 10 days abolished the effect of adrenalectomy and decreased significantly pituitary VIP mRNA content in sham-operated rats. In the cerebral cortex, however, dexamethasone treatment resulted in an enhancement in VIP mRNA levels in both sham-operated and adrenalectomized animals. Hypothalamic VIP mRNA content remained unchanged. These changes in VIP mRNA levels were accompanied by parallel changes in VIP concentrations in the tissues studied, suggesting that glucocorticoid regulates the synthesis of VIP in the cerebral cortex and anterior pituitary. On the other hand, serum PRL level increased after adrenalectomy but became suppressed following dexamethasone administration, in parallel with changes in pituitary VIP synthesis. These findings suggest that the effect of glucocorticoid on PRL secretion may be mediated, at least in part, via changes in VIP synthesis and secretion. We conclude that glucocorticoid regulates the expression of VIP in the rat brain, resulting in divergent changes in the cerebral cortex and pituitary. Changes in VIP synthesis and secretion may contribute to the disturbances in brain function and PRL secretion in conditions of glucocorticoid excess.