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Corticotropin-Releasing Factor (CRF) and the Urocortins Differentially Regulate Catecholamine Secretion in Human and Rat Adrenals, in a CRF Receptor Type-Specific Manner

Departments of Clinical Chemistry-Biochemistry (E.D., C.T., M.V., A.A., A.N.M.), Pharmacology (V.M., I.C., A.G.), and Forensic Sciences (E.M.), School of Medicine, University of Crete, Heraklion GR-710 03, Crete, Greece; Departments of Pharmacology (E.C.) and Histology-Embryology (M.L.), School of Medicine, Democritus University of Thrace, Alexandroupolis, GR-68 100, Greece; Department of Neuroscience (J.S.), J. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii 96822

Address all correspondence and requests for reprints to: Andrew N. Margioris, Department of Clinical Chemistry-Biochemistry, School of Medicine, University of Crete, Heraklion GR-710 03, Crete, Greece. E-mail: andym{at}med.uoc.gr.

Corticotropin-releasing factor (CRF) affects catecholamine production both centrally and peripherally. The aim of the present work was to examine the presence of CRF, its related peptides, and their receptors in the medulla of human and rat adrenals and their direct effect on catecholamine synthesis and secretion. CRF, urocortin I (UCN1), urocortin II (UCN2), and CRF receptor type 1 (CRF₁) and 2 (CRF₂) were present in human and rat adrenal medulla as well as the PC12 pheochromocytoma cells by immunocytochemistry, immunofluorescence, and RT-PCR. Exposure of dispersed human and rat adrenal chromaffin cells to CRF₁ receptor agonists induced catecholamine secretion in a dose-dependent manner, an effect peaking at 30 min, whereas CRF₂ receptor agonists suppressed catecholamine secretion. The respective effects were blocked by CRF₁ and CRF₂ antagonists. CRF peptides affected catecholamine secretion via changes of subplasmaliminal actin filament polymerization. CRF peptides also affected catecholamine synthesis. In rat chromaffin and PC12 cells, CRF₁ and CRF₂ agonists induced catecholamine synthesis via tyrosine hydroxylase. However, in human chromaffin cells, activation of CRF₁ receptors induced tyrosine hydroxylase, whereas activation of CRF₂ suppressed it. In conclusion, it appears that a complex intraadrenal CRF-UCN/CRF-receptor system exists in both human and rat adrenals controlling catecholamine secretion and synthesis.