EXOCRINE GLAND DYSFUNCTION IN MC5-R-DEFICIENT MICE - EVIDENCE FOR COORDINATED REGULATION OF EXOCRINE GLAND-FUNCTION BY MELANOCORTIN PEPTIDES

The effects of pituitary-derived melanocortin peptides are primarily a ttributed to ACTH-mediated adrenocortical glucocorticoid production. I dentification of a widely distributed receptor for ACTH/MSH peptides, the melanocortin-5 receptor (MC5-R), suggested non-steroidally mediate d systemic effects of these peptides. Targeted disruption of the MC5-R produced mice with a severe defect in water repulsion and thermoregul ation due to decreased production of sebaceous lipids. High levels of MC5-R was found in multiple exocrine tissues, including Harderian, pre putial, lacrimal, and sebaceous glands, and was also shown to be requi red for production and stress-regulated synthesis of porphyrins by the Harderian gland and ACTH/MSH-regulated protein secretion by the lacri mal gland. These data show a requirement for the MC5-R in multiple exo crine glands for the production of numerous products, indicative of a coordinated system for regulation of exocrine gland function by melano cortin peptides.