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DOI: 10.1055/s-2004-814341
Elevated Ghrelin Plasma Levels in Patients with Polycystic Ovary Syndrome
Publication History
Received 4 June 2003
Accepted after second revision 27 October 2003
Publication Date:
01 April 2004 (online)
![](https://www.thieme-connect.de/media/hmr/200403/lookinside/thumbnails/10.1055-s-2004-814341-1.jpg)
Abstract
Polycystic ovary syndrome is a common endocrine disorder in women. It is associated with hirsuitism, obesity, insulin resistance, abnormality in the growth hormone/insulin-like growth factor I (IGF-1) axis and polycystic ovaries. The etiology of PCOS has not been clarified. Ghrelin is an endogenous ligand of the growth hormone secretagogue receptor. It is mainly secreted by stomach cells but has also been shown to be present in hypothalamus, pituitary, pancreas and gonads. Ghrelin is a regulator of energy homeostasis and GH secretion. The influence of ghrelin on insulin secretion and gonadal function is known. Since ghrelin may play an important role in pathophysiology of PCOS, we studied ghrelin levels in a group of 52 women with PCOS and in 16 women in a control group. Plasma levels of insulin, total testosterone, SHBG, LH, and FSH were also measured. In conclusion, PCOS women have higher ghrelin levels than controls. Ghrelin negatively correlates with BMI and insulin levels in PCOS group. A relation between ghrelin and SHBG was observed. Our data suggest that ghrelin could be the possible link in PCOS etiology.
Key words
Women - Insulin - Obesity - Androgens - Growth hormone - Insulin-like growth factor I axis
References
- 1 Knochenhauer E S, Key T J, Kahsar-Miller M, Waggoner W, Boots L, Azziz R. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: prospective study. J Clin Endocrinol Metab. 1998; 83 3078-3082
- 2 Franks S. Polycystic ovary syndrome. N Engl J Med. 1995; 333 853-861
- 3 Gambineri A, Pagotto U, Pelusi C, Vicennati V, Pasquali R. Obesity and the polycystic ovary syndrome. Int J Obes. 2002; 26 883-896
- 4 Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev. 1997; 18 774-800
- 5 Dunaif A. Insulin action in the polycystic ovary syndrome. J Clin Endocrinol Metab. 1999; 28 340-359
- 6 Urbanek M, Legro R S, Driscoll D A, Azziz R, Ehrmann D A, Norman R J, Strauss J F, Spielman R S, Dunaif A. Thirty-seven candidate genes for polycystic ovary syndrome: Strongest evidence for linkage is follistatin. Proc Natl Acad Sci. 1999; 96 8573-8578
- 7 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
- 8 Dornonville de la Cour C, Bjorkqvist M, Sandvik A K. et al . A-like cells in rat stomach contain ghrelin and do not operate under gastrin control. Regul Pept. 2001; 99 141-150
- 9 Date Y, Kojima M, Hosoda H. et al . Ghrelin, a novel growth hormone acyclated peptide, is synthesized in the gastrointestinal tract of rats and humans. Endocrinol. 2000; 141 4255-4261
- 10 Kagotani Y, Sakata I, Yamazaki M, Nakamura K, Hayashi Y, Kangawa K. Localization of ghrelin-immunopositive cells in the rat hypothalamus and intestinal tract. Proceedings of the 83rd Annual Meeting of the Endocrine Society, Denver, CO. 2001: 337
- 11 Karbonits M, Kojima M, Kangawa K, Grossman A B. Presence of ghrelin in normal and adenomatous human pituitary. Endocrine. 2001; 14 101-104
- 12 Wierup N, Svensson H, Mulder H, Sundler F. The ghrelin cell: a novel developmentally regulated islet cell in the human pancreas. Regul Pept. 2002; 107 63-69
- 13 Tena-Sempere M, Barreiro M L, Gonzales L C, Gaytan F, Zhang F P, Caminos J E, Pinilla L, Casanueva F F, Dieguez C, Aguilar E. Novel expression and functional role of ghrelin in rat testis. Endocrinology. 2002; 143 717-725
- 14 Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, Matsukura S. A role for ghrelin in the central regulation of feeding. Nature. 2001; 409 194-198
- 15 Arvat E, Di Vito L, Broglio F. et al . Preeliminary evidence that ghrelin, the natural GH secretagogue (GHS)-receptor ligand, strongly stimulates GH secretion in humans. J Endocrinol Invest. 2000; 23 493-495
- 16 Tschőp M, Smiley D L, Heiman M L. Ghrelin induces adiposity in rodents. Nature. 2000; 407 908-913
- 17 Horvath T L, Diano S, Sotonyi P, Heiman M, Tschöp M. Minireview: ghrelin and the regulation of energy balance - A hypothalamic perspective. Endocrinology. 2001; 142 4163-4169
- 18 Wren A M, Small C J, Abbott C R, Dhillo W S, Seal L J, Cohen M A. Ghrelin causes hyperphagia and obesity in rats. Diabetes. 2001; 50 2540-2547
- 19 Ott V, Fasshauer M, Dalski A, Meier B, Perwitz N, Klein H H, Tschöp M, Klein J. Direct peripherial effects of ghrelin include suppression of adiponectin expression. Horm Metab Res. 2002; 34 640-645
- 20 Takaya K, Ariyasu H, Kanamoto N, Iwakura H, Yoshimoto A, Harada M, Mori K, Komatsu Y, Usui T, Shimatsu A, Ogawa Y, Hosoda K, Akamizu T, Kojima M, Kangawa K, Nakao K. Ghrelin strongly stimulates growth hormone (GH) release in humans. J Clin Endocr Metab. 2000; 85 4908-4911
- 21 Stefan N, Stumvoll M. Adiponectin - its role in metabolism and beyond. Horm Metab Res. 2002; 34 469-474
- 22 Möhling M, Wegewitz U, Osterhoff M, Isken F, Ristow M, Pfeiffer A FH, Spranger J. Insulin decreases human adiponectin plasma levels. Horm Metab Res. 2002; 34 655-658
- 23 Barreiro M L, Pinilla L, Aguilar E, Tena-Sampere M. Expression and homologous regulation of GH secretagogue receptor m RNA in rat adrenal gland. Eur J Endocrinol. 2002; 147 677-688
- 24 Tschöp M, Weyer C, Tataranni P A, Devanarayan V, Ravussin E, Heiman M L. Circulating ghrelin levels are decreased in human obesity. Diabetes. 2001; 50 707-709
- 25 Ariayasu H, Takaya K, Tagami T. et al .Plasma ghrelin levels are influenced by acute and chronic feeding states in humans. Proceedings of the 83rd Annual Meeting of the Endocrine Society, Denver, CO. 2001: 336
- 26 Orio F, Lucidi P, Palomba S, Tauchmanova L, Cascella T, Russo T, Zullo F, Colao A, Lombardi G, De Feo P. Circulating ghrelin concentrations in polycystic ovary syndrome. J Clin Endocrinol Metab. 2003; 88 942-945
- 27 Pagotto U, Gambineri A, Vicennati V, Heiman M L, Tschöp M, Pasquali R. Plasma ghrelin, obesity, and the polycystic ovary syndrome: correlation with insulin resistance and androgen levels. J Clin Endocrinol Metab. 2002; 87 5625-5629
- 28 Schöfl C, Rüdiger H, Schill T, Schlösser H W, Müller M J, Brabant G. Circulating ghrelin levels in patients with polycystic ovary syndrome. J Clin Endocrinol Metab. 2002; 87 4607-4610
- 29 Piaditis G P, Kounadi T G, Rangou D B, Trovas G P, Kaklas N A, Tzonou A J, Chlouverakis C S. Dysfunction of the growth hormone/insulin-like factor I axis in women with polycystic ovarian syndrome. J Clin Endocrinol Metab. 1995; 42 635-640
- 30 Słowińska-Strzednicka J, Zgliczyński W, Makowska A, Jeske W, Brzezińska A, Soszyński P, Zgliczyński S. An abnormality of the growth hormone/insulin-like growth factor-I axis in women with polycystic ovary syndrome due to coexistent obesity. J Clin Endocrinol Metab. 1992; 74 1432-1435
- 31 Lanzone A, Villa P, Fulghesu A M, Pavone V, Caruso A, Mancuso S. The growth hormone response to growth hormone - releasing hormone is blunted in polycystic ovary syndrome: relationship with obesity and hyperinsulinaemia. Hum Reprod. 1995; 10 1653-1657
- 32 Lee H, Wang G, Englander E W, Kojima M, Greeley G H Jr. Ghrelin a new gastrointestinal endocrine peptide that stimulates insulin secretion: enteric distribution ontogeny influence of endocrine and dietary manipulations. Endocrinology. 2002; 143 185-190
- 33 Date Y, Nakazato M, Hashiguchi S, Dezaki K, Mondal M S, Hosoda H, Kojima M, Kangawa K, Arima T, Matsuo H, Yada T, Matsukura S. Ghrelin is present in pancreatic α-cells of humans and rats and stimulates insulin secretion. Diabetes. 2002; 51 124-129
- 34 Egido E M, Rodriguez-Gallardo J, Gutierrez E, Garcia P, Silverstre R A, Marco J. Inhibitory effect of ghrelin on insulin secretion in the rat pancreas. Diabetologia. 2001; 44 (Supl. 1) A 135 (Abstract)
R. Waśko, M. D.
Department of Endocrinology and Metabolism · University of Medical Sciences Poznań
Ul. Przybyszewskiego 49 · 60-355 Poznań · Poland
Phone: +48(61)86913 32
Fax: +48(61)8691682
Email: endonucl@mail.am.poznan.pl