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Circulating Ghrelin Levels in Patients with Polycystic Ovary Syndrome

Abteilung Gastroenterologie, Hepatologie und Endokrinologie (C.S., R.H., G.B.), Abteilung Reproduktion und Fertilität (T.S., H.W.S.), Medizinische Hochschule Hannover, D-30623 Hannover, Germany; and Institut für Humanernährung und Lebensmittelkunde, Christian-Albrecht-Universität (M.J.M.), D-24098 Kiel, Germany

Address all correspondence and requests for reprints to: Georg Brabant, Abteilung Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Carl-Neubergstrasse 1., D-30623 Hannover, Germany. E-mail: Brabant.georg{at}mh-hannover.de.

Abstract

The syndrome of polycystic ovaries (PCOS) is associated with adiposity and metabolic changes predisposing to insulin resistance and diabetes mellitus. Because the recently discovered GH secretagogue, ghrelin, is intimately involved in the control of appetite and weight regulation, we studied ghrelin levels in a group of 26 otherwise healthy women with PCOS. They were compared with 61 healthy female control subjects and 5 gastrectomized women. Insulin sensitivity was assessed by homeostasis model assessment (HOMA) and continuous infusion of glucose with model assessment (CIGMA) in all patients. In PCOS women, serum ghrelin levels were significantly lower than in healthy lean or obese controls (P < 0.001). In insulin-sensitive PCOS women, ghrelin concentrations compared well with the healthy controls, whereas in insulin-resistant PCOS ghrelin levels were significantly lower and indistinguishable from the low levels found in the gastrectomized women. There was a close correlation of ghrelin to insulin sensitivity (HOMA, r² = 0.330, P < 0.002; CIGMA, r² = 0.568, P < 0.0001). Treatment of 10 insulin-resistant PCOS women with metformin significantly increased circulating fasting ghrelin concentrations (P < 0.02). Ghrelin levels did not correlate to any of the parameters of hyperandrogenemia, to the LH/FSH ratio, to body mass index, or to fasting insulin and glucose concentrations. In summary, ghrelin levels are decreased in PCOS women and are highly correlated to the degree of insulin resistance. This suggests that ghrelin could be linked to insulin resistance in PCOS women. However, whether low ghrelin in PCOS is a cause or the consequence of insulin resistance awaits further investigations.

POLYCYSTIC OVARY SYNDROME (PCOS) is one of the most frequent endocrine disorders in women. It is clinically characterized by hirsutism, chronic anovulation, and infertility (1, 2). Diagnosis is based on clinical symptoms, increased androgen levels, and an increased LH/FSH ratio in the absence of other specific adrenal, ovarian, or pituitary causes such as 21-hydroxylase deficiency, androgen-secreting tumors, or hyperprolactinemia (2). Only recently, the metabolic aspects of PCOS have been established. PCOS women are predisposed to adiposity and insulin resistance, and prospective studies demonstrate a high risk for impaired glucose tolerance and type 2 diabetes mellitus (3). The mechanisms, however, linking PCOS to these metabolic changes are only partly clarified.

Ghrelin, a 28-amino acid peptide recently isolated from rat and human stomach, is the long-searched natural ligand for the GH secretagogue receptor (4). One of the most important biological activities of ghrelin reported so far is the stimulation of food intake and long-term regulation of body weight (4, 5, 6, 7, 8, 9, 10). Physiologically, ghrelin levels rise shortly before a meal and drop rapidly after a meal (9, 10, 11). Ingestion of glucose but not water or protein reduces circulating ghrelin by 30–50% (Refs. 9, 10, 11, 12 and our unpublished data). Consistent with a role in the control of food intake, short-term ghrelin application in man directly stimulates appetite for several hours and reduces postprandial satiety (8). Long-term infusion of ghrelin in animal models via centrally stimulating food intake increases body fat accumulation and causes adiposity (5, 6, 7). In humans in states of chronic malnutrition such as anorexia nervosa, serum ghrelin levels are increased (13), whereas obesity is associated with decreased ghrelin concentrations that increase after weight loss (10, 12, 14, 15, 16).

Because PCOS women are predisposed to obesity and to metabolic changes such as insulin resistance, we measured serum ghrelin in 26 women with PCOS and compared them to 61 healthy female control subjects. Serum ghrelin levels were significantly lower in PCOS patients compared with healthy controls, and this was strongly related to the degree of insulin resistance.

Subjects and Methods

Twenty-six women diagnosed with PCOS were included in the study after informed consent was obtained. The diagnosis was based on clinical symptoms (oligomenorrhea, hirsutism) and laboratory findings (elevated serum androgen levels and/or elevated LH/FSH ratio). Cushing’s syndrome, late-onset 21-hydroxylase deficiency, thyroid dysfunction, hyperprolactinemia, or androgen-secreting tumors were excluded. The clinical and endocrine features of the women are given in Table 1. Two patients suffered from Hashimoto's thyroiditis. They were euthyroid under thyroid hormone replacement therapy. All other patients were free of other diseases and were taking no medications. Ten insulin-resistant PCOS women were reevaluated after 5–6 months of treatment with 850 mg metformin thrice daily.

Fasting blood samples of 61 healthy female blood donors with no known medication or menstrual disorders (mean age, 28.9 ± 0.7 yr; mean BMI, 23.3 ± 0.4 kg/m²) were analyzed for serum ghrelin concentrations and served as normal controls. In addition, serum ghrelin levels were determined in five women gastrectomized for gastric cancer who were in a stable remission (time of operation, more than 5 yr earlier; no current drug treatment for more than 6 months; mean age, 72 ± 3.6 yr; mean BMI, 23.4 ± 2.6 kg/m²).

Assays

Blood glucose was measured by the glucose dehydrogenase method (Hoffmann-La Roche, Grenzach, Germany). Serum insulin was measured by a commercial RIA (Pharmacia, Freiburg, Germany) with a lower limit of sensitivity of less than 14 pmol/liter and intra- and interassay coefficients of variation (CV) of 5.8% and 5.8%, respectively. Serum 17-OH-progesterone was determined by RIA (Schering, Berlin, Germany) with a lower level of sensitivity 2 ng/100 ml and intra- and interassay CV of 3.2% and 3.9%, respectively. Serum LH and progesterone were measured by chemiluminescence immunoassays using kits obtained from Bayer Diagnostics (Fernwald, Germany). The intra- and interassay CV were 2.9% and 2.4%, respectively, for LH, and 3.7% and 3.9% for progesterone, and the minimal detectable concentrations were 0.07 mU/ml (LH) and 0.15 ng/ml (progesterone). Dehydroepiandrosterone sulfate (DHEAS) was assayed by a chemiluminescence immunoassay purchased from Nichols Institute Diagnostics (Bad Nauheim, Germany) with a lower sensitivity 10 ng/ml and intra- and interassay CV of 7.1% and 9.0%, respectively. Serum FSH was determined by an immunoradiometric assay (BioChem ImmunoSystems, Freiburg, Germany) with a lower sensitivity of 0.3 mU/ml and inter- and intra-assay CV of 2% and 3.1%, respectively. Estradiol (E₂), testosterone (T), and SHBG were measured by RIA obtained from Diagnostic Systems Laboratories, Inc. (Sinsheim, Germany) with lower detectable concentrations of 2.2 pg/ml, 0.08 ng/ml, and 0.4 µg/ml, respectively. The respective inter- and intra-assay CV were 2.2% and 2.7% for E₂, 9.6% and 8.6% for T, and 2.2% and 4.4% for SHBG. Androstendione was determined by RIA (Coulter Immunotech, Marseille, France) with a lower sensitivity of 4 ng/100 ml and inter- and intra-assay CV of 5.6% and 6%, respectively.

A RIA procedure was used to measure serum ghrelin levels. Ghrelin antiserum was generated in rabbits using a synthetic C-terminal fragment (amino acids 15–28, 14Tyr, Biotrend, Köln, Germany) coupled to hemocyanin. A working titer of 1:1200 was used for subsequent studies. Tracer generated by the iodogen method was HPLC-purified on a C18 column. Full-length ghrelin (Bachem, Heidelberg, Germany) was used as a standard. Antibody-bound fraction and free peptide were separated by 2% dextrancharcoal (methodology analogous to Ref. 18). There was parallelism between diluted high ghrelin serum samples and the standard curve. No cross-reactivity was shown to related peptides such as motilin, to GHRH or leptin. The interassay CV was 4.1%, the intra-assay CV was 2.6%, and the detection limit was 34 pmol/liter. Serum ghrelin was stable when stored at -20 C.

Statistics

Data are presented as the mean ± SEM. Statistical analysis was performed by the two-tailed paired or unpaired t test. Least squares regression analysis was performed using StatView software for the Macintosh (Abacus Concepts, Berkeley, CA). The level of significance was taken as P value less than 0.05.

Results

Serum ghrelin concentrations averaged 181 ± 14 pmol/liter (range, 108–386 pmol/liter; n = 26) in the patients with PCOS, which was significantly lower than in the healthy blood donors (224 ± 8 pmol/liter; n = 61; P < 0.005). Seventeen PCOS women were classified as insulin resistant and 9 as insulin sensitive, according to HOMA/CIGMA assessment (Table 1). In the insulin-sensitive PCOS women, ghrelin levels were similar to the ones in the healthy controls (Fig. 1A). By contrast, ghrelin concentrations were significantly decreased in the insulin-resistant PCOS patients compared with healthy controls or insulin-sensitive PCOS women (Fig. 1A). The mean ghrelin serum levels in the insulin-resistant group compared well with the low ghrelin concentrations in gastrectomized women (Fig. 1A). Fasting ghrelin correlated neither to BMI, fasting insulin, and glucose, nor to glucose concentrations reached after the 2-h glucose infusion. They were weakly and negatively correlated to insulin levels stimulated by the 2-h glucose infusion but closely correlated to the degree of insulin sensitivity as assessed by HOMA or CIGMA (Table 2 and Fig. 1B). In 10 PCOS women treated with metformin for 5–6 months, serum ghrelin levels significantly increased (P < 0.02; Fig. 1C).

View larger version (17K): [in this window] [in a new window]   Figure 1. Serum ghrelin and insulin resistance. A, Ghrelin concentrations in healthy controls, insulin-sensitive and insulin-resistant PCOS subjects, and gastrectomized women. Values are means ± SEM. ***, P < 0.001 for insulin-sensitive PCOS or healthy blood donors vs. insulin-resistant PCOS or gastrectomized women; n.s., not significant. B, Correlation between serum ghrelin and insulin sensitivity (%S) as assessed by CIGMA in 26 PCOS women. C, Effect of metformin treatment for 5–6 months on ghrelin levels in insulin-resistant PCOS patients (n = 10). In seven of them, %S was reassessed by CIGMA after 6 months of therapy. *, P < 0.05; **, P < 0.02.

Discussion

PCOS is related to obesity and to major metabolic alterations including both insulin resistance and ß-cell dysfunction (1, 2, 19). Here, we show that serum levels of the recently characterized endogenous GH secretagogue, ghrelin, are significantly lower in women suffering from PCOS than in controls. The levels are in the range of the ghrelin nadir in healthy subjects during an oral glucose tolerance test in which ghrelin drops by approximately 30% (Refs. 10, 11, 12 and our unpublished data). No relation was found to hyperandrogenemia or any other sex steroid.

Seventeen PCOS women were insulin resistant as judged by HOMA/CIGMA. In these insulin-resistant subjects, ghrelin concentrations were even lower and matched the ghrelin levels found in gastrectomized women. Serum ghrelin, however, was comparable to healthy control subjects in the insulin-sensitive PCOS women. A positive and highly significant correlation of ghrelin concentrations to the degree of insulin resistance was found in PCOS subjects. Furthermore, insulin-resistant PCOS patients treated with metformin, which improves insulin sensitivity in PCOS patients (20), increased serum ghrelin levels. This suggests a link between insulin sensitivity and ghrelin concentrations and shows that the dysregulated ghrelin system in insulin-resistant PCOS women could be normalized by metformin therapy.

Ghrelin concentrations have been reported to be correlated to BMI with reduced levels in obesity that increase in response to weight loss (10, 12, 14, 15). In the present study, both in PCOS patients and normal controls, ghrelin tended to relate to BMI, but this did not reach statistical significance. This discrepancy might be explained by the relatively narrow BMI range in our subjects compared with those reported by others (12, 14). Because obesity is associated with insulin resistance (21), the possibility exists that the correlation observed between BMI and ghrelin may reflect a variation in insulin sensitivity, which was not measured directly in the previous studies (10, 12, 14, 16, 21). The fact, however, that ghrelin closely correlated to the degree of insulin resistance but not to BMI in our subjects may indicate that factors other than simple adiposity could determine ghrelin levels. Many observations support interactions between ghrelin, insulin, and carbohydrate metabolism. However, the exact nature of these interactions is not yet clarified, and conflicting results have been reported. In vivo infusion of ghrelin acutely increases serum glucose levels and decreases insulin secretion (22). Because ghrelin is expressed in pancreatic islet-cells, it may exert direct inhibitory actions on insulin release (23). Other in vivo and in vitro data suggest a stimulatory action of ghrelin on insulin release (24, 25). On the other hand, insulin stimulates up-regulation of ghrelin mRNA in the stomach in vitro, but in vivo iv insulin has no impact on circulating ghrelin levels in humans, further demonstrating a complex interplay between both hormones (11, 26). In our PCOS patients, ghrelin did not correlate to fasting glucose or to insulin, which argues against a simple mechanism explaining the decrease in serum ghrelin in insulin-resistant PCOS women. It remains unclear whether ghrelin is directly linked to insulin sensitivity via an insulin-mediated process or via other mechanisms associated with insulin resistance such as elevated free fatty acids. This may be supported by previous observations in PCOS patients showing elevated circulating FFA levels and by a suppressive effect of a high-fat diet on fasting ghrelin levels in rats (27, 28).

In summary, ghrelin levels are decreased in PCOS women and are highly correlated to the degree of insulin resistance. This indicates that ghrelin, apart from its role in the control of appetite and body weight could be linked to insulin resistance. However, whether low ghrelin in PCOS is a cause or the consequence of insulin resistance awaits further investigations.

Acknowledgments

Footnotes

Abbreviations: BMI, Body mass index; CIGMA, continuous infusion of glucose with model assessment; CV, coefficient(s) of variation; DHEAS, dehydroepiandrosterone sulfate; E₂, estradiol; HOMA, homeostasis model assessment; PCOS, polycystic ovary syndrome; T, testosterone.

Received March 31, 2002.

Accepted June 28, 2002.

References

1. Franks S 1995 Polycystic ovary syndrome. N Engl J Med 333:853–861[Free Full Text]
2. Dunaif A 1997 Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 18:774–800[Abstract/Free Full Text]
3. Legro RS, Kunselman AR, Dodson WC, Dunaif A 1999 Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab 84:165–169[Abstract/Free Full Text]
4. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K 1999 Ghrelin is a novel growth hormone releasing acylated peptide from stomach. Nature 402:656–660[CrossRef][Medline]
5. Tschöp M, Smiley DL, Heiman ML 2000 Ghrelin induces adiposity in rodents. Nature 407:908–913[CrossRef][Medline]
6. Wren AM, Small CJ, Abbott CR, Dhillo WS, Seal LJ, Cohen MA, Batterham RL, Taheri S, Stanley SA, Ghatei MA, Bloom SR 2001 Ghrelin causes hyperphagia and obesity in rats. Diabetes 50:2540–2547[Abstract/Free Full Text]
7. Tschöp M, Statnick MA, Suter TM, Heiman ML 2002 GH-releasing peptide-2 increases fat mass in mice lacking NPY: indication for a crucial mediating role of hypothalamic agouti-related protein. Endocrinology 143:558–568[Abstract/Free Full Text]
8. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR 2001 Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 86:599–604
9. Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS 2001 A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 50:1714–1719[Abstract/Free Full Text]
10. Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, Purnell JQ 2002 Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 346:1623–1630[Abstract/Free Full Text]
11. Caixás A, Bashore C, Nash W, Pi-Sunyer F, Laferrére B 2002 Insulin, unlike food intake, does not suppress ghrelin in human subjects. J Clin Endrocrinol Metab 87:1902–1906[Abstract/Free Full Text]
12. Shiiya T, Nakazato M, Mizuta M, Date Y, Mondal MS, Tanaka M, Nozoe S, Hosoda H, Kangawa K, Matsukura S 2002 Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab 87:240–244[Abstract/Free Full Text]
13. Otto B, Cuntz U, Fruehauf E, Wawarta R, Folwaczny C, Riepl RL, Heiman ML, Lehnert P, Fichter M, Tschop M 2001 Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa. Eur J Endocrinol 145:669–673[Abstract]
14. Tschöp M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML 2001 Circulating ghrelin levels are decreased in human obesity. Diabetes 50:707–709[Abstract/Free Full Text]
15. Hansen TK, Dall R, Hosoda H, Kojima M, Kangawa K, Christiansen JS, Jorgensen JO 2002 Weight loss increases circulating levels of ghrelin in human obesity. Clin Endocrinol (Oxf) 56:203–206[CrossRef][Medline]
16. English PJ, Ghatei MA, Malik IA, Bloom SR, Wilding JPH 2002 Food fails to suppress ghrelin levels in obese humans. J Clin Endocrinol Metab 87:2984–2987[Abstract/Free Full Text]
17. Hermans MP, Levy JC, Morris RJ, Turner RC 1999 Comparison of insulin sensitivity tests across a range of glucose tolerance from normal to diabetes. Diabetologia 42:678–687[CrossRef][Medline]
18. Horn R, Geldszus R, Potter E, von zur Mühlen A, Brabant G 1996 Radioimmunoassay for the detection of leptin in human serum. Exp Clin Endocrinol Diabetes 104:454–458[Medline]
19. Dunaif A, Finegood DT 1996 ß-Cell dysfunction independent of obesity and glucose intolerance in the polycystic ovary syndrome. J Clin Endocrinol Metab 81:942–947[Abstract]
20. Moghetti P, Castello R, Negri C, Tosi F, Perrone F, Caputo M, Zanolin E, Muggeo M 2000 Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation. J Clin Endocrinol Metab 85:139–146[Abstract/Free Full Text]
21. Steppan CM, Lazar MA 2002 Resistin and obesity-associated insulin resistance. Trends Endocrinol Metab 13:18–23[CrossRef][Medline]
22. Broglio F, Arvat E, Benso A, Gottero C, Muccioli G, Papotti M, van der Lely AJ, Deghenghi R, Ghigo E 2001 Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans. J Clin Endocrinol Metab 86:5083–5086[Abstract/Free Full Text]
23. Egido EM, Rodriguez-Gallardo J, Silvestre RA, Marco J 2002 Inhibitory effect of ghrelin on insulin and pancreatic somatostatin secretion. Eur J Endocrinol 146:241–244[Abstract]
24. Lee H, Wang G, Englander EW, Kojima M, Greeley Jr GH 2002 Ghrelin, a new gastrointestinal endocrine peptide that stimulates insulin secretion: enteric distribution, ontogeny, influence of endocrine, and dietary manipulations. Endocrinology 143:185–190[Abstract/Free Full Text]
25. Date Y, Nakazato M, Hashiguchi S, Dezaki K, Mondal MS, Hosoda H, Kojima M, Kangawa K, Arima T, Matsuo H, Yada T, Matsukura S 2002 Ghrelin is present in pancreatic -cells of humans and rats and stimulates insulin secretion. Diabetes 51:124–129[Abstract/Free Full Text]
26. Toshinai K, Mondal MS, Nakazato M, Date Y, Murakami N, Kojima M, Kangawa K, Matsukura S 2001 Upregulation of ghrelin expression in the stomach upon fasting, insulin-induced hypoglycemia, and leptin administration. Biochem Biophys Res Commun 281:1220–1225[CrossRef][Medline]
27. Holte J, Bergh T, Berne C, Lithell H 1994 Serum lipoprotein lipid profile in women with the polycystic ovary syndrome: relation to anthropometric, endocrine and metabolic variables. Clin Endocrinol (Oxf) 41:463–471[Medline]
28. Beck B, Musse N, Stricker-Krongrad A 2002 Ghrelin, macronutrient intake and dietary preferences in long-evans rats. Biochem Biophys Res Commun 292:1031–1035[CrossRef][Medline]

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				C. Anderwald, G. Brabant, E. Bernroider, R. Horn, A. Brehm, W. Waldhausl, and M. Roden Insulin-Dependent Modulation of Plasma Ghrelin and Leptin Concentrations Is Less Pronounced in Type 2 Diabetic Patients Diabetes, July 1, 2003; 52(7): 1792 - 1798. [Abstract] [Full Text] [PDF]

				P. U. Freda, C. M. Reyes, I. M. Conwell, R. E. Sundeen, and S. L. Wardlaw Serum Ghrelin Levels in Acromegaly: Effects of Surgical and Long-Acting Octreotide Therapy J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2037 - 2044. [Abstract] [Full Text] [PDF]

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