Active Ghrelin Levels in Women with Polycystic Ovary Syndrome

Re: Wasko R, Komarowska H, Warenik-Szymankiewicz A, Sowinski J. Elevated ghrelin plasma levels in patients with polycystic ovary syndrome. Horm Metab Res 2004; 36 : 170 - 173.

An interesting study on ghrelin plasma levels in patients with polycystic ovary syndrome (PCOS) was recently published by Wasko et al. [1]. I would like to point out some observations that may improve our understanding of ghrelin’s role in women with PCOS.

Ghrelin is a 28-amino acid peptide with a unique serine residue at the third position (Ser³); posttranslational esterification with octanoic acid of this residue is essential for binding to type 1a growth hormone secretagogue receptor and subsequent ghrelin biological activity, such as GH release from the pituitary gland [2].

The polyclonal antibody used by the authors (Phoenix Pharmaceutical, Belmont, CA, USA) does not distinguish octanoylated and non-octanoylated ghrelin. Importantly, non-octanoylated ghrelin does not activate type 1a growth hormone secretagogue receptor [3] [4] and is presumed to be inactive [2]. Therefore, the authors measured the total ghrelin levels in women with PCOS, but they could not evaluate the levels of active ghrelin; this limit in their study is particularly relevant, as non-octanoylated ghrelin is far more abundant than active octanoylated ghrelin [3].

Interestingly, Linco Research (St Charles, MO, USA) produces an antibody that is specific for the biologically active form of ghrelin with the octanoyl group on serine 3 (cat. no. GHRA-88HK). The active ghrelin form is very unstable and labile in plasma due to the nature of the octanoyl group on serine-3; as a consequence, special precautions must be taken. In particular, the samples should be kept on ice and processed as quickly as possible after blood is withdrawn. In addition, plasma acidification is recommended.

Measuring both total and biologically active ghrelin concentrations may improve our understanding of the role of this hormone in women with PCOS.

References

• 1 Wasko R, Komarowska H, Warenik-Szymankiewicz A, Sowinski J. Elevated ghrelin plasma levels in patients with polycystic ovary syndrome.  Horm Metab Res. 2004;  36 170-173
• 2 Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach.  Nature. 1999;  402 656-660
• 3 Hosoda H, Kojima M, Matsuo H, Kangawa K. Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue.  Biochem Biophys Res Commun. 2000;  279 909-913
• 4 Bednarek M A, Feighner S D, Pong S S, McKee K K, Hreniuk D L, Silva M V, Warren V A, Howard A D, Van Der Ploeg L H, Heck J V. Structure-function studies on the new growth hormone-releasing peptide, ghrelin: minimal sequence of ghrelin necessary for activation of growth hormone secretagogue receptor 1a.  J Med Chem. 2000;  43 4370-4376