The Effect of alpha MSH Analogues on Rat Bones.
10.3349/ymj.2002.43.4.500
- Author:
Sung Kil LIM
1
;
Song Zhe LI
;
Yumie RHEE
;
Sang Su CHUNG
;
Yong Jun JIN
;
Jong In YOOK
Author Information
1. Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea. lsk@yumc.yonsei.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
alpha MSH;
bone mineral density;
osteoclast
- MeSH:
Animal;
Body Weight/drug effects;
Bone and Bones/*drug effects;
CHO Cells;
Cyclic AMP/biosynthesis;
Eating/drug effects;
Hamsters;
Male;
Osteoblasts/drug effects/physiology;
Osteoclasts/drug effects/physiology;
Rats;
Rats, Sprague-Dawley;
Receptors, Corticotropin/physiology;
alpha-MSH/analogs & derivatives/*pharmacology
- From:Yonsei Medical Journal
2002;43(4):500-510
- CountryRepublic of Korea
- Language:English
-
Abstract:
Melanocortin is the downstream mediator of leptin signaling and absence of leptin signaling in ob/ob and db/db mice revealed the enhancement of bone formation through the central regulation. While alpha-melanocyte-stimulating hormone (alpha MSH) inhibits the secretion of interleukin-1 alpha and tumor necrosis factor-alpha from the inflammatory cells, alpha MSH can also enhance clonal expansion of pro B cells linked to stimulation of osteoclastogenesis. Therefore, we tested the effect of melanocortin on bones. alpha MSH analogues [6His] alpha MSH-ND and [6Asn] alpha MSH-ND were synthesized and the radio-ligand receptor binding- and cyclic AMP generating activity were analyzed in China Hamster Ovary cell line over- expressing melanocortin receptors. The EC50 of [6His] alpha MSH-ND measured from melanocortin-1, 3, 4 and 5 receptors were 0.008 0.0045, 1.523 0.707, 0.780 0.405, and 250.320 42.234 nM, respectively, and the EC50 of [6Asn] alpha MSH-ND were 16.8 6.94, 271.8 21.95, 8.0 1.21, and 1132.5 635.46 nM, respectively. Four weeks after the subcutaneous injection of the analogues, the body weights in the [6His] alpha MSH-ND and the [6Asn] alpha MSH-ND treated groups (346.0 20.63 g vs. 350.0 13.57 g) were lower than that of the vehicle treated group (375.8 17.31 g, p 0.05). There was no difference in the total femoral BMD measured by dual x-ray absorptiometry among the three groups. Among the three groups, there were no differences in the total numbers of crystal violet positive- or alkaline phosphatase positive colonies, in the expression of Receptor Activator of Nuclear Factor Kappa-B ligand on the tibia and the total number of multinucleated osteoclast-like cells differentiated from primary cultured bone marrow cells. From the above results, no evidence of bone gain or loss was found after treatment of the alpha MSH analogues peripherally.
