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 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.
Chen
W
W
Vollum Institute, Oregon Health Sciences University, Portland 97201, USA.
Kelly
M A
MA
Opitz-Araya
X
X
Thomas
R E
RE
Low
M J
MJ
Cone
R D
RD
D000818:Animals; D001833:Body Temperature Regulation; D005088:Exocrine Glands / Q000502:physiology*; D005260:Female; D015698:Genomic Library; D006243:Harderian Gland / Q000502:physiology; D007765:Lacrimal Apparatus / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009928:Organ Specificity; D010413:Penis; D011166:Porphyrins / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D018043:Receptors, Corticotropin / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D044101:Receptors, Melanocortin; D012627:Sebaceous Glands / Q000502:physiology; D014158:Transcription, Genetic; D014162:Transfection
D011166:Porphyrins; D012333:RNA, Messenger; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; C086971:melanocortin 5 receptor