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Rudolf Magnus Institute for Neurosciences, Department of Medical Pharmacology, Utrecht University, 3508 TA Utrecht, The Netherlands; and the Division of Endocrinology, Diabetes, Metabolism, and Molecular Medicine, Department of Medicine, and the Tupper Research Institute, Tufts University School of Medicine and New England Medical Center Hospitals (M.L.E., J.B.T.), Boston, Massachusetts 02111
Address all correspondence and requests for reprints to: Dr. Roger A. H. Adan, Rudolf Magnus Institute for Neurosciences, Department of Medical Pharmacology, Utrecht University, P.O. Box 80040, 3508 TA Utrecht, The Netherlands. E-mail: R.A.H.Adan{at}med.ruu.nl
Melanocortins (
MSH and ACTH-related peptides) influence the
physiological functions of certain peripheral organs, including
exocrine and endocrine glands. This study was designed to determine the
identity and anatomical localization of the melanocortin receptors
(MC-R) expressed in these organs in the rat. MC5-R messenger RNA was
found in exocrine glands, including lacrimal, Harderian, preputial, and
prostate glands and pancreas, as well as in adrenal gland, esophagus,
and thymus, as demonstrated by ribonuclease protection assays. In
exocrine glands, MC5-R messenger RNA expression was restricted to
secretory epithelia. MC-R protein was likewise present in secretory
epithelia of exocrine glands, as determined by 125I-labeled
[Nle4,D-Phe7]MSH
([125I]NDP-MSH) binding and autoradiography in tissue
sections. Specific [125I]NDP-MSH binding was also
observed in adrenal cortex, thymus, spleen, and esophageal and
trachealis muscle. MC receptors in these sites are accessible to
circulating MC-R agonists in vivo, as specific binding
of [125I]NDP-MSH was observed in exocrine and adrenal
glands after systemic injection in vivo. Taken together,
these findings show that the MC5 receptor is commonly and selectively
expressed in exocrine glands and other peripheral organs. Based on
these findings and compelling evidence from other studies, a functional
coherence is suggested between central and peripheral actions of
melanocortins and melanocortin receptors in physiological functions,
including thermoregulation, immunomodulation, and sexual behavior.
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