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Letter re: Melanin-Concentrating Hormone and Energy Balance

Department of Biochemistry and Molecular Biology, Neurogen Corporation, Branford, Connecticut 06405

Address correspondence to: Stephen M. Waters, Ph.D., Neurogen Corporation, Department of Biochemistry and Molecular Biology, 35 NE Industrial Road, Branford, Connecticut 06405. E-mail: swaters{at}nrgn.com.

To the editor:

In their article entitled "Circulating melanin-concentrating hormone, agouti-related protein, and -melanocyte-stimulating hormone levels in relation to body composition: Alterations in response to food deprivation and recombinant human leptin administration" (1), Gavrila et al. report the use of a commercially available melanin-concentrating hormone (MCH) RIA (Phoenix Pharmaceuticals, Belmont, CA) to determine human serum MCH levels. Their findings are potentially of great interest in that MCH may serve as a biomarker for fat mass status and response to dietary alterations and pharmacotherapy. Because this commercial RIA has not been validated for plasma or serum samples, this report should have included additional data, as required in the "Instructions to Authors," including assay specificity, parallelism of standard compared with unknown, and correlation with an independent assay method. It has been our experience that commercially available MCH antisera can cross-react with an additional substance(s) in human, rat, or mouse serum. We have tested antisera from Phoenix Pharmaceuticals and Sigma (St. Louis, MO) using serum from wild-type mice and mice in which the MCH gene coding region has been deleted (2). [Wild-type and MCH knockout mouse serum was generously provided by Dr. Eleftheria Maratos-Flier.] Using either antisera, both wild-type and MCH knockout mouse sera contain an immunoreactive substance(s), suggesting that these antisera are not specific for MCH. Additionally, in parallelism analyses of standard compared with unknown, we do not observe increased radiotracer displacement using human, rat, or mouse serum/plasma input greater than 25 µl (B/Bo = 50–70%). Furthermore, the authors state that the Phoenix Pharmaceuticals assay has a sensitivity of 70 pg/ml, yet they report levels as low as 20 ± 7 pg/ml in their interventional study (see Table 3 in Ref.1). Phoenix Pharmaceuticals claims an average detection limit of only 17 pg/tube or 170 pg/ml.

Based on the authors’ results, there does appear to be an MCH antisera cross-reacting substance(s) in serum that may be coordinately regulated by fat mass and affected by fasting. However, this substance has not been shown to be authentic MCH. We caution against the interpretation by the authors that serum MCH levels can be easily measured and may currently be used as a marker in the diagnosis and therapy of obese individuals. Until more selective and sensitive reagents are available to measure authentic serum or plasma MCH, the use of serum or plasma MCH immunoreactivity as an obesity biomarker in humans or experimental animals is not a valid approach.

Received June 21, 2005.

References

1. Gavrila A, Chan JL, Miller LC, Heist K, Yiannakouris N, Mantzoros CS 2005 Circulating melanin-concentrating hormone, agouti-related protein, and -melanocyte-stimulating hormone levels in relation to body composition: alterations in response to food deprivation and recombinant human leptin administration. J Clin Endocrinol Metab 90:1047–1054[Abstract/Free Full Text]
2. Shimada M, Tritos NA, Lowell BB, Flier JS, Maratos-Flier E 1998 Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature 396:670–674[CrossRef][Medline]

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