title: Melanocortin-5 receptor and sebogenesis.
abstract: The melanocortins (α-MSH, β-MSH, γ-MSH, and ACTH) bind to the melanocortin receptors and signal through increases in cyclic adenosine monophosphate to induce biological effects. The melanocortin MC(5) and MC(1) receptors are expressed in human sebaceous glands, which produce sebum, a lipid mixture of squalene, wax esters, triglycerides, cholesterol esters, and free fatty acids that is secreted onto the skin. Excessive sebum production is one of the major factors in the pathogenesis of acne. The expression of melanocortin MC(5) receptor has been associated with sebocyte differentiation and sebum production. Sebaceous lipids are down-regulated in melanocortin MC(5) receptor-deficient mice, consistent with the observation that α-MSH acts as a sebotropic hormone in rodents. These findings, which suggest that melanocortins stimulate sebaceous lipid production through the MC(5) receptor, led to our search for MC(5) receptor antagonists as potential sebum-suppressive agents. As predicted, an antagonist was shown to inhibit sebocyte differentiation in vitro, and to reduce sebum production in human skin transplanted onto immunodeficient mice. The melanocortin MC(5) receptor antagonists may prove to be clinically useful for the treatment of sebaceous disorders with excessive sebum production, such as acne.
authors.affiliation: The Johnson & Johnson Skin Research Center, Consumer Product Worldwide, a unit of Johnson & Johnson Consumer Companies, Inc.,199 Grandview Rd., Skillman, NJ 08558, USA. lzhang1@its.jnj.com
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Wen-Hwa
authors.initials: WH
authors.lastname: Li
authors.forename: Michael
authors.initials: M
authors.lastname: Anthonavage
authors.forename: Apostolos
authors.initials: A
authors.lastname: Pappas
authors.forename: Dianne
authors.initials: D
authors.lastname: Rossetti
authors.forename: Druie
authors.initials: D
authors.lastname: Cavender
authors.forename: Miri
authors.initials: M
authors.lastname: Seiberg
authors.forename: Magdalena
authors.initials: M
authors.lastname: Eisinger
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000096:biosynthesis; D008962:Models, Theoretical; D044101:Receptors, Melanocortin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012627:Sebaceous Glands / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D012629:Sebum / Q000187:drug effects / Q000378:metabolism
chemical_list: D008055:Lipids; D044101:Receptors, Melanocortin; C086971:melanocortin 5 receptor