1. Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides.
- Author
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Chen W, Kelly MA, Opitz-Araya X, Thomas RE, Low MJ, and Cone RD
- Subjects
- Animals, Body Temperature Regulation, Female, Genomic Library, Harderian Gland physiology, Lacrimal Apparatus physiology, Male, Mice, Mice, Knockout, Mice, Transgenic, Organ Specificity, Penis, Porphyrins metabolism, RNA, Messenger biosynthesis, Rats, Receptors, Corticotropin biosynthesis, Receptors, Melanocortin, Sebaceous Glands physiology, Transcription, Genetic, Transfection, Exocrine Glands physiology, Receptors, Corticotropin deficiency, Receptors, Corticotropin genetics
- Abstract
The effects of pituitary-derived melanocortin peptides are primarily attributed to ACTH-mediated adrenocortical glucocorticoid production. Identification of a widely distributed receptor for ACTH/MSH peptides, the melanocortin-5 receptor (MC5-R), suggested non-steroidally mediated systemic effects of these peptides. Targeted disruption of the MC5-R produced mice with a severe defect in water repulsion and thermoregulation due to decreased production of sebaceous lipids. High levels of MC5-R was found in multiple exocrine tissues, including Harderian, preputial, lacrimal, and sebaceous glands, and was also shown to be required for production and stress-regulated synthesis of porphyrins by the Harderian gland and ACTH/MSH-regulated protein secretion by the lacrimal gland. These data show a requirement for the MC5-R in multiple exocrine glands for the production of numerous products, indicative of a coordinated system for regulation of exocrine gland function by melanocortin peptides.
- Published
- 1997
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