title: alpha -melanocyte-stimulating hormone is a novel regulator of bone.
abstract: alpha-Melanocyte-stimulating hormone (alpha-MSH), a 13-amino acid peptide produced in the brain and pituitary gland, is a regulator of appetite and body weight, and its production is regulated by leptin, a factor that affects bone mass when administered centrally. alpha-MSH acts via melanocortin receptors. Humans deficient in melanocortin receptor 4 (MC4-R) have increased bone mass, and MC4-R has been identified in an osteoblast-like cell line. Thus alpha-MSH may act directly on the skeleton, a question addressed by the present studies. In primary cultures of osteoblasts and chondrocytes, alpha-MSH dose dependently (>or=10(-9) M) stimulated cell proliferation. In bone marrow cultures, alpha-MSH (>10(-9) M) stimulated osteoclastogenesis. Systemic administration of alpha-MSH to mice (20 injections of 4.5 microg/day) decreased the trabecular bone volume in the proximal tibiae from 19.5 +/- 1.8 to 15.2 +/- 1.4% (P = 0.03) and reduced trabecular number (P = 0.001). Radiographic indexes of trabecular bone, assessed by phase-contrast X-ray imaging, confirmed the bone loss. It is concluded that alpha-MSH acts directly on bone, increasing bone turnover, and, when administered systemically, it decreases bone volume. The latter result may also be contributed to by alpha-MSH effects elsewhere, such as the adipocyte, pancreatic beta-cell, or central nervous system.
authors.affiliation: Department of Medicine, University of Auckland, Auckland 1001, New Zealand. j.cornish@auckland.ac.nz
authors.forename: Jillian
authors.initials: J
authors.lastname: Cornish
authors.forename: Karen E
authors.initials: KE
authors.lastname: Callon
authors.forename: Kathleen G
authors.initials: KG
authors.lastname: Mountjoy
authors.forename: Usha
authors.initials: U
authors.lastname: Bava
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Lin
authors.forename: Damian E
authors.initials: DE
authors.lastname: Myers
authors.forename: Dorit
authors.initials: D
authors.lastname: Naot
authors.forename: Ian R
authors.initials: IR
authors.lastname: Reid
mesh_terms: D000818:Animals; D001823:Body Composition; D001846:Bone Development / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D008858:Microscopy, Phase-Contrast; D009924:Organ Culture Techniques; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D051381:Rats; D000521:alpha-MSH / Q000494:pharmacology*
chemical_list: D000521:alpha-MSH; D002118:Calcium