Urocortin messenger ribonucleic acid: Tissue distribution in the rat and regulation in thymus by lipopolysaccharide and glucocorticoids

Urocortin (Ucn), a new mammalian member of the CRF family, is a candidate e ndogenous ligand for type 2 CRF receptors. In a survey of peripheral tissue s from adult male rats, we found that Ucn messenger RNA (mRNA) was abundant in the gastrointestinal tract and immune tissues such as thymus and spleen . We next tested the hypothesis that levels of Ucn mRNA levels in thymus an d spleen would be altered after immune activation. As measured by riboncule ase protection assay, lipopolysaccharide (LPS) induced a a-fold time-depend ent increase in thymic Ucn mRNA levels within 6 h. By contrast, splenic Ucn mRNA levels decreased after LPS. Because LPS activates the hypothalamus-pi tuitary-adrenal (HPA) axis, we examined whether the effects of LPS on Ucn m RNA might be mediated through changes in HPA axis hormones. Ucn mRNA in thy mus, but not spleen, was significantly increased after ACTH injection; howe ver, LPS did not increase Ucn expression in the thymus of adrenalectomized rats with corticosterone replacement, despite substantial increases in ACTH . Finally, sc injection of corticosterone stimulated Ucn mRNA comparably to that of LPS. Together, these results suggest that Ucn mRNA expression can increase after immune activation in a corticosterone-dependent manner, and that such changes in Ucn mRNA may be an additional consequence of HPA axis activation.