N-Octanoylated Ghrelin Levels in Cord and Neonatal Blood

Simone Ferrero

Department of Obstetrics and Gynaecology, San Martino Hospital, University of Genoa, 16132 Genoa, Italy

Address correspondence to: Simone Ferrero, Department of Obstetrics and Gynaecology, San Martino Hospital, University of Genoa, Largo R. Benzi 1, 16132 Genoa, Italy. E-mail: simone.ferrero{at}fastwebnet.it.

To the editor:

I read with interest the article by Kitamura et al. (1) correlating ghrelin concentration in cord and neonatal blood with fetal growth and energy balance. I would like to bring to your attention some methodological concerns that have arisen.

Ghrelin is a peptide of 28 amino acids, and it requires posttranslational n-octanoyl modification of a serine residue for its activity (2, 3). This acylation enables the binding to type 1a GH secretagogue receptor that is essential for the biological functions of the hormone (2). Nonoctanoylated ghrelin does not activate type 1a GH secretagogue receptor (4, 5), and it is presumed to be inactive (2).

The polyclonal antibodies used by the authors to measure plasma ghrelin do not distinguish octanoylated and nonoctanoylated ghrelin, and, as a consequence, the total ghrelin level was measured. However, a monoclonal antibody specific for the active form of ghrelin (with the octanoyl group on serine 3) is commercially available (Linco Research, St. Charles, MO; catalog no. GHRA-88HK). I believe that the measurement of total ghrelin should always be associated to the determination of the biologically active ghrelin concentration. Special precautions are required when the active form of ghrelin is measured because it is very unstable and labile in plasma; the samples should be kept in ice and processed as quickly as possible after blood is withdrawn; the plasma should be acidified.

The authors found no correlation between total ghrelin and GH in cord blood. Also, no relationship was observed between ghrelin concentrations in neonates and mean daily body weight gain during the first month of life. I believe that these observations should be confirmed by measuring the active n-octanoylated ghrelin levels.

In conclusion, further studies are required to elucidate the role of active n-octanoylated ghrelin during fetal and neonatal life and to evaluate the correlation of its levels with GH secretion.

Received February 22, 2004.

References

  1. Kitamura S, Yokota I, Hosoda H, Kotani Y, Matsuda J, Naito E, Ito M, Kangawa K, Kuroda Y 2003 Ghrelin concentration in cord and neonatal blood: relation to fetal growth and energy balance. J Clin Endocrinol Metab 88:5473–5477[Abstract/Free Full Text]
  2. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K 1999 Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402:656–660[CrossRef][Medline]
  3. Hosoda H, Kojima M, Matsuo H, Kangawa K 2000 Purification and characterization of rat des-Gln14-ghrelin, a second endogenous ligand for the growth hormone secretagogue receptor. J Biol Chem 275:21995–22000[Abstract/Free Full Text]
  4. Hosoda H, Kojima M, Matsuo H, Kangawa K 2000 Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun 279:909–913[CrossRef][Medline]
  5. Bednarek MA, Feighner SD, Pong SS, McKee KK, Hreniuk DL, Silva MV, Warren VA, Howard AD, Van Der Ploeg LH, Heck JV 2000 Structure-function studies on the new growth hormone-releasing peptide, ghrelin: minimal sequence of ghrelin necessary for activation of the growth hormone secretagogue receptor 1a. J Med Chem 43:4370–4376[CrossRef][Medline]




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