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Horm Metab Res 2010; 42(4): 274-279
DOI: 10.1055/s-0029-1243260
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Plasma Sex Hormone-binding Globulin, Corticosteroid-binding Globulin, Cortisol, and Free Cortisol Levels in Outpatients Attending a Lipid Disorders Clinic: A Cross-sectional Study of 1137 Subjects

J. G. Lewis1 , K. K. Borowski1 , B. I. Shand2 , P. M. George1 , R. S. Scott2
  • 1Department of Clinical Biochemistry, Canterbury Health Laboratories, Christchurch, New Zealand
  • 2Lipid and Diabetes Research Group, Christchurch Hospital, Christchurch, New Zealand
Further Information

Publication History

received 04.06.2009

accepted 23.11.2009

Publication Date:
07 January 2010 (online)

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Abstract

We measured plasma sex hormone-binding globulin (SHBG), corticosteroid-binding globulin (CBG), and total cortisol, and calculated free plasma cortisol in 1 137 subjects attending a hospital outpatient lipid disorders clinic to investigate whether or not these analytes correlated with the degree of insulin resistance and the presence of the metabolic syndrome. In both males and females, plasma SHBG correlated inversely with anthropometric measures and with fasting glucose, insulin, insulin resistance, and triglycerides, and positively with HDL-cholesterol. However, in males with the metabolic syndrome, unlike females, the relationship between SHBG, some anthropometric measures, fasting glucose, insulin, and HDL-cholesterol were lost, which suggests that in males SHBG may not co-cluster with other components of the metabolic syndrome. In males and males with the metabolic syndrome, total plasma cortisol and calculated plasma free cortisol correlated positively with fasting glucose. Corticosteroid-binding globulin correlated inversely with percentage body fat and positively with HDL-cholesterol in males with and without the metabolic syndrome. CBG correlated negatively with age in both sexes. Overall, the results confirm the finding that SHBG is a marker of insulin resistance in males and females and that SHBG is associated with fasting triglycerides in males with the metabolic syndrome. Importantly, SHBG could be considered a stronger component of the metabolic syndrome in females than in males. However, the aetiological role of CBG and cortisol in insulin resistance is uncertain, although in males, cortisol and CBG could be subtly related to the degree of insulin resistance.

Key words

SHBG - CBG - cortisol - free cortisol - plasma - insulin resistance - glucose - insulin - metabolic syndrome

References

  • 1 Katsuki A, Sumida Y, Murashima S, Fujii M, Ito K, Tsuchihashi K, Murata K, Yano Y, Shima T. Acute and chronic regulation of serum sex hormone-binding globulin levels by male noninsulin-dependent diabetes mellitus patients.  J Clin Endocrinol Metab. 1996;  81 2515-2519
    Google Scholar
  • 2 Muller M, Grobbee DE, Tonkelaar den I, Lamberts SWJ, Schouw van der YT. Endogenous sex hormones and metabolic syndrome in aging men.  J Clin Endocrinol Metab. 2005;  90 2618-2623
    Google Scholar
  • 3 Lewis JG, Shand BI, Elder PA, Scott RS. Plasma sex hormone-binding globulin rather than corticosteroid-binding globulin is a marker of insulin resistance in obese adult males.  Diabet Obes Metab. 2004;  6 259-283
    Google Scholar
  • 4 Tchernof A, Despres JP. Sex steroid hormones, sex hormone-binding globulin, and obesity in men and women.  Horm Metab Res. 2000;  32 526-536
    Google Scholar
  • 5 Laaksonen DE, Niskanen L, Punnonen K, Nyyssönen K, Tuomainen T-P, Salonen R, Rauramaa R, Salonen JT. Sex hormones, inflammation and the metabolic syndrome: a population-based study.  Eur J Endocrinol. 2003;  149 601-608
    Google Scholar
  • 6 Reed MJ, Cheng RW, Simmonds M, Richmond W, James VH. Dietary lipids: an additional regulator of plasma levels of sex hormone-binding globulin.  J Clin Endocrinol Metab. 1987;  64 1083-1085
    Google Scholar
  • 7 Plymate SR, Matej LA, Jones RE, Friedl KE. Inhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin.  J Clin Endocrinol Metab. 1988;  67 460-464
    Google Scholar
  • 8 Maggio M, Lauretani F, Basaria S, Ceda GP, Bandinelli S, Metter EJ, Bos AJ, Rugiero C, Ceresini G, Paolisso G, Artoni A, Valenti G, Guralnik JM, Ferrucci L. Sex hormone-binding globulin levels across the adult lifespan in women: the role of body mass index and fasting insulin.  J Endocrinol Invest. 2008;  31 597-601
    Google Scholar
  • 9 Jayagopal V, Kilpatrick ES, Jennings PE, Holding S, Hepburn DA, Atkin SL. The biological variation of sex hormone-binding globulin in Type 2 diabetes.  Diabetes Care. 2004;  27 278-280
    Google Scholar
  • 10 McElduff A, Hitchman, R, McElduff P. Is sex hormone-binding globulin associated with glucose tolerance?.  Diabetic Medicine. 2005;  23 306-312
    Google Scholar
  • 11 Haffner SM, Katz MS, Stern MP, Dunn JF. Relationship of sex hormone-binding globulin to overall adiposity and body fat distribution in a biethnic population.  Int J Obes. 1989;  13 1-9
    Google Scholar
  • 12 Crave JC, Lejeune H, Brebant C, Baret C, Pugeat M. Differential effects of insulin and insulin-like growth factor 1 on the production of plasma steroid-binding globulins by human hepatoblastoma-derived (Hep G2) cells.  J Clin Endocrinol Metab. 1995;  80 1283-1289
    Google Scholar
  • 13 Fernández-Real J-M, Pugeat M, Emptoz-Bonneton A, Ricart W. Study of the effect of changing glucose, insulin, and insulin-like growth factor-I levels on serum corticosteroid-binding globulin in lean, obese, and obese subjects with glucose intolerance.  Metabolism. 2001;  50 1248-1252
    Google Scholar
  • 14 Fernández-Real J-M, Pugeat M, Grasa M, Broch M, Vendrell J, Brun J, Ricart W. Serum corticosteroid-binding globulin concentration and Insulin Resistance Syndrome: A population study.  J Clin Endocrinol Metab. 2002;  87 4680-4690
    Google Scholar
  • 15 Lewis JG, Möpert B, Shand BI, Doogue MP, Soule SG, Frampton CM, Elder PA. Plasma variation of corticosteroid-binding globulin and sex hormone-binding globulin.  Horm Metab Res. 2006;  38 241-245
    Google Scholar
  • 16 Lewis JG, Shand BI, Frampton CM, Elder PA, Scott RS. Plasma levels of sex hormone-binding globulin, corticosteroid-binding globulin and cortisol in overweight subjects who develop impaired fasting glucose: a 3-year prospective study.  Horm Metab Res. 2009;  41 255-259
    Google Scholar
  • 17 Lewis JG, Longley NJ, Elder PA. Monoclonal antibodies to human sex hormone-binding globulin (SHBG): Characterization and use in a simple enzyme-linked immunosorbent assay (ELISA) of SHBG in plasma.  Steroids. 1999;  64 259-265
    Google Scholar
  • 18 Lewis JG, Lewis MG, Elder PA. An enzyme-linked immunosorbent assay for corticosteroid-binding globulin using monoclonal and polyclonal antibodies: decline in CBG following synthetic ACTH.  Clin Chim Acta. 2003;  328 121-128
    Google Scholar
  • 19 Lewis JG, Manley L, Whitlow JC, Elder PA. Production of a monoclonal antibody to cortisol: application to a direct enzyme-linked immunosorbent assay of plasma.  Steroids. 1992;  57 82-85
    Google Scholar
  • 20 Coolens J-L, Van Baelen H, Heyns W. Clinical use of unbound plasma cortisol as calculated from total cortisol and corticosteroid-binding globulin.  J Steroid Biochem. 1987;  26 197-202
    Google Scholar
  • 21 Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program.  Diabetes Care. 1998;  21 2191-2192
    Google Scholar
  • 22 Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation.  Diabet Med. 1998;  15 539-553
    Google Scholar
  • 23 Executive summary of the third report of the national Cholesterol Education Program (NECP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III).  JAMA. 2001;  285 2486-2497
    Google Scholar
  • 24 Muller M, den Tonkelaar I, Thijssen JHH, Grobbee DE, van der Schouw YT. Endogenous sex hormones in men aged 40-80 years.  Eur J Endocrinol. 2003;  149 583-589
    Google Scholar
  • 25 Weinberg ME, Manson JE, Buring JE, Cook NR, Seely, EW, Ridker PM, Rexrode KM. Low sex hormone-binding globulin is associated with the metabolic syndrome in postmenopausal women.  Metab Clin Exp. 2006;  55 1473-1480
    Google Scholar
  • 26 Haffner SM, Valdez RA, Morales PA, Hazuda HP, Stern MP. Decreased sex hormone-binding globulin predicts noninsulin-dependent diabetes mellitus in women but not in men.  J Clin Endocrinol Metab. 1993;  77 56-60
    Google Scholar
  • 27 Selva DM, Hogeveen KN, Innis SM, Hammond GL. Monosaccharide-induced lipogenesis regulates the human hepatic sex-hormone-binding globulin gene.  J Clin Invest. 2007;  117 3979-3987
    Google Scholar
  • 28 Hautanen A. Synthesis and regulation of sex hormone-binding globulin in obesity.  Int J Obes Relat Metab Disord. 2000;  24 S64-S70
    Google Scholar
  • 29 Chubb SAP, Hyde Z, Almeida OP, Flicker L, Norman PE, Jamrozik K, Hankey GJ, Yeap BB. Lower sex hormone-binding globulin is more strongly associated with metabolic syndrome than lower testosterone in older men: the Health in Men Study.  Eur J Endocrinol. 2008;  158 785-792
    Google Scholar
  • 30 Bataille V, Perret B, Evans A, Amouyel P, Arveiler D, Ducimetière P, Bard J-M, Ferrières J. Sex hormone-binding globulin is a major determinant of the lipid profile: the PRIME study.  Atherosclerosis. 2005;  179 369-373
    Google Scholar
  • 31 Laaksonen DE, Niskanen L, Punnonen K, Nyyssönen K, Tuomainen T-P, Valkonen V-P, Salonen R, Salonen JT. Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men.  Diabetes Care. 2004;  27 1036-1041
    Google Scholar
  • 32 Pasquali R, Vicennati V. Steroids and the metabolic syndrome.  J Steroid Biochem Mol Biol. 2008;  109 258-265
    Google Scholar
  • 33 Fernández-Real J-M, Pugeat M, López-Bermejo A, Bornet H, Ricart W. Corticosteroid-binding globulin affects the relationship between circulating adiponectin and cortisol in men and women.  Metab Clin Exper. 2005;  54 584-589
    Google Scholar
  • 34 Araki T, Emoto M, Konishi T, Ikuno Y, Lee E, Teramura M, Motoyama K, Yokoyama H, Mori K, Koyama H, Shoji T, Nishizawa Y. Glimepiride increases high-density lipoprotein cholesterol via increasing adiponectin levels in type 2 diabetes mellitus.  Metab Clin Exper. 2009;  58 143-148
    Google Scholar
  • 35 Schulze MB, Rimm EB, Shai IS, Rifai N, Hu FB. Relationship between adiponectin and glycemic control, blood lipids, and inflammatory markers in men with type 2 diabetes.  Diabetes Care. 2004;  27 1680-1687
    Google Scholar
  • 36 Reynolds RM, Walker BR. Can cortisol predict the future in obesity?.  Clin Endocrinol. 2007;  67 1-2
    Google Scholar
  • 37 Holt HB, Wild SH, Postle AD, Zhang J, Koster G, Umpleby M, Shojaee-Moradie F, Dewbury K, Wood PJ, Phillips DI, Byrne CD. Cortisol clearance and associations with insulin sensitivity, body fat and fatty liver in middle-aged men.  Diabetologia. 2007;  50 1024-1032
    Google Scholar
  • 38 Wang M. The role of glucocorticoid action in the pathophysiology of the metabolic syndrome.  Nutr Metab. 2005;  2 3-16
    Google Scholar
  • 39 Walker BR. Glucocorticoids and cardiovascular disease.  Eur J Endocrinol. 2007;  157 545-559
    Google Scholar
  • 40 Wiegratz I, Kutschera E, Lee JH, Moore C, Mellinger U, Winkler UH, Kuhl H. Effect of four different oral contraceptives on various sex hormones and serum-binding globulins.  Contraception. 2003;  67 25-32
    Google Scholar
  • 41 Santini SA, Carrozza C, Lulli P, Zuppi C, Tonolo GC, Musumeci S. Atorvastatin treatment does not affect gonal or adrenal hormones in type 2 diabetes patients with mild to moderate hypercholesterolemia.  J Artheroscler Thromb. 2003;  10 160-164
    Google Scholar
  • 42 Hacihanefioglu B, Somunkiran A, Mahmutoglu I, Sercelik A, Toptani S, Kervancioglu E. Effect of hypertension therapy with the angiotensin-converting enzyme inihibitor lisinopril on hyperandrogenism in women with polycystic ovary syndrome.  Fertil Steril. 2002;  77 526-528
    Google Scholar
  • 43 Gambineri A, Pelusi C, Genghini S, Morselli-Labate AM, Cacciari M, Pagotto U, Pasquali R. Effect of flutamide and metformin administered alone or in combination in dieting obese women with polycystic ovary syndrome.  Clin Endocrinol. 2004;  60 241-249
    Google Scholar
  • 44 Stroud LR, Solomon C, Shenassa E, Papandonatos G, Niaura R, Lipsitt LP, LeWinn K, Buka SL. Long-term stability of maternal prenatal steroid hormones from the National Collaborative Perinatal Project: Still valid after all these years.  Psychoneuroendocrinol. 2007;  32 140-150
    Google Scholar

Correspondence

J. G. Lewis

Department of Clinical Biochemistry

Canterbury Health Laboratories

P. O. Box 151

Christchurch

New Zealand

Phone: +64 3 3640 877

Fax: +64 3 3640 889

Email: john.lewis@cdhb.govt.nz