The effect of alphaMSH analogues on rat bones.

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 (alphaMSH) inhibits the secretion of interleukin-1alpha and tumor necrosis factor-alpha from the inflammatory cells, alphaMSH can also enhance clonal expansion of pro B cells linked to stimulation of osteoclastogenesis. Therefore, we tested the effect of melanocortin on bones. alphaMSH analogues [(6)His]alphaMSH-ND and [(6)Asn]alphaMSH-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 EC(50) of [(6)His]alphaMSH-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 EC(50) of [(6)Asn]alphaMSH-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 [(6)His]alphaMSH-ND and the [(6)Asn]alphaMSH-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 alphaMSH analogues peripherally.

• Authors: Sung-Kil Lim, Song-Zhe Li, Yumie Rhee, Sang Su Chung, Yong-Jun Jin, Jong In Yook
• Journal: Yonsei medical journal (Yonsei Med J) Vol. 43 Issue 4 Pg. 500-10 (Aug 2002) ISSN: 0513-5796 [Print] Korea (South)
• PMID: 12205739 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Corticotropin
• Receptors, Melanocortin
• melanocortin 5 receptor
• alpha-MSH
• Cyclic AMP

Topics

• Animals
• Body Weight (drug effects)
• Bone and Bones (drug effects)
• CHO Cells
• Cricetinae
• Cyclic AMP (biosynthesis)
• Eating (drug effects)
• Male
• Osteoblasts (drug effects, physiology)
• Osteoclasts (drug effects, physiology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Corticotropin (physiology)
• Receptors, Melanocortin
• alpha-MSH (analogs & derivatives, pharmacology)