Expression of melanocortin 5 receptor in secretory epithelia supports a functional role in exocrine and endocrine glands

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 behavio

Expression of melanocortin receptors and pro-opiomelanocortin in the rat spinal cord in relation to neurotrophic effects of melanocortins

Although neurotrophic effects of -melanocyte-stimulating hormone (-MSH) are well established, the mechanism underlying these effects is unknown. To identify candidate components of the signaling system that may mediate these effects, in the present study rat spinal cord, dorsal root ganglia, sciatic nerve and soleus muscle were analysed for the expression of the neural MC3, MC4 and MC5 receptors and for the expression of the melanocortin precursor pro-opiomelanocortin (POMC). In rat lumbar spinal cord, the MC4 receptor was the only MC receptor subtype for which mRNA was detectable using RNAse protection assays. In situ binding studies using 125I-NDP-MSH, a synthetic -MSH analogue, demonstrated MC receptor protein in the rat spinal cord, predominantly localised in substantia gelatinosa and area X, surrounding the central canal. Furthermore, POMC mRNA was demonstrated in rat spinal cord and dorsal root ganglia. These findings suggest a functional melanocortin system in the rat spinal cord, that might be involved in peripheral nerve repair. Regulation of POMC or MC receptor transcripts does not appear to be involved in the response to peripheral nerve crush in rats, since no change in mRNA expression patterns was detected after sciatic nerve crush, using quantitative RNAse protection assays. Nevertheless, subtle changes in melanocortin receptor binding did occur postsurgically in several regions of the spinal cord in both sham-operated and sciatic nerve-lesioned rats. The robust expression of MC receptor protein in spinal cord regions that are generally associated with nociception suggests a potentially broader involvement of endogenous melanocortins in spinal pathways which mediate the responses to peripheral injury, in addition to any direct melanocortin effects on sprouting and neurite outgrowth