Article
Licensed
Unlicensed Requires Authentication

Unchanged androgen-binding properties of sex hormone-binding globulin in male patients with liver cirrhosis

  • , , , , and
Published/Copyright: September 21, 2011
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 44 Issue 8

Abstract

Background: Men affected by liver cirrhosis frequently show clinical features of hypogonadism due to hormonal changes, in particular in the metabolism of 17β-estradiol (E2) and testosterone (T). Sex hormone-binding globulin (SHBG), the major binding protein of these steroids in serum, is regularly elevated in such patients, with its androgen-binding properties possibly altered. In the present study, surface plasmon resonance biosensor techniques were used to determine whether the functional binding properties of this transporter are maintained in this pathology.

Methods: We selected 33 male patients with cirrhosis, Child-Pugh grade A or B, and 32 healthy males served as controls. Serum concentrations of T, E2, dehydroepiandrosterone sulfate (DHEAS) and SHBG were measured. In addition, ligand-binding properties of SHBG partially purified from sera of 23 cirrhotic patients and 20 controls were analyzed by a real-time biosensor technique using a surface-coated dihydrotestosterone derivative.

Results: The sensorgrams revealed that SHBG was fully bioactive in all samples investigated without any changes in binding kinetics. Moreover, total T concentrations were not significantly different in the cirrhotic patient sera (mean±SD 18.0±8.6nmol/L) compared to controls (15.6±3.7; n.s.), whereas E2 was higher (152±60 vs. 96±29pmol/L; p<0.0001) and DHEAS was lower (1493±1410 vs. 5099±2844 nmol/L; p<0.0001).

Conclusions: Owing to elevated SHBG levels without changes in the steroid-binding properties in sera of cirrhotic male patients, free or bioavailable T concentrations are lower. This causes a shift of the hormonal balance in favor of E2, which exhibits a lower affinity for SHBG than androgens and accounts for the endocrine symptoms.

Clin Chem Lab Med 2006;44:967–73.

Keywords: androgen metabolism; liver cirrhosis; sex hormone-binding globulin (SHBG); surface plasmon resonance biosensor
Corresponding author: Prof. Dr. Peter B. Luppa, Institute of Clinical Chemistry and Pathobiochemistry, Ismaninger Str. 22, 81675 Munich, Germany Phone: +49-89-4140-4759, Fax: +49-89-4140-4875,

References

1. Johnson PJ. Sex hormones and liver. Clin Sci 1984; 66:369–76.10.1042/cs0660369Search in Google Scholar

2. Longcope C, Pratt JH, Schneider S, Fineberg E. Estrogen and androgen dynamics in liver disease. J Endocrinol Invest 1984; 7:629–33.10.1007/BF03349497Search in Google Scholar

3. Karagiannis A, Harsoulis F. Gonadal dysfunction in systemic diseases. Eur J Endocrinol 2005; 152:501–13.10.1530/eje.1.01886Search in Google Scholar

4. Tanaka K, Sakai H, Hashizume M, Hirohata T. Serum testosterone/estradiol ratio and the development of hepatocellular carcinoma among male cirrhotic patients. Cancer Res 2000; 60:5106–10.Search in Google Scholar

5. Nolte W, Schindler CG, Figulla HR, Wuttke W, Hufner M, Hartmann H, et al. Increase of serum estradiol in cirrhotic men treated by transjugular intrahepatic portosystemic stent shunt. J Hepatol 2001; 34:818–24.10.1016/S0168-8278(01)00052-6Search in Google Scholar

6. Bannister P, Losowsky MS. Sex hormones and chronic liver disease. J Hepatol 1988; 6:258–62.10.1016/S0168-8278(88)80039-4Search in Google Scholar

7. Van Thiel DH, Gavaler JS, Spero JA, Egler KM, Wright C, Sanghvi AT, et al. Patterns of hypothalamic-pituitary-gonadal dysfunction in men with liver disease due to differing etiologies. Hepatology 1981; 1:39–46.10.1002/hep.1840010107Search in Google Scholar PubMed

8. De Besi L, Zucchetta P, Zotti S, Mastrogiacomo I. Sex hormones and sex hormone binding globulin in males with compensated and decompensated cirrhosis of the liver. Acta Endocrinol (Copenh) 1989; 120:271–6.10.1530/acta.0.1200271Search in Google Scholar PubMed

9. Iturriaga H, Lioi X, Valladares L. Sex hormone-binding globulin in non-cirrhotic alcoholic patients during early withdrawal and after longer abstinence. Alcohol Alcohol 1999; 34:903–9.10.1093/alcalc/34.6.903Search in Google Scholar PubMed

10. Terasaki T, Nowlin DM, Pardridge WM. Differential binding of testosterone and estradiol to isoforms of sex-hormone-binding globulin: selective alteration of estradiol binding in cirrhosis. J Clin Endocrinol Metab 1988; 67:639–43.10.1210/jcem-67-4-639Search in Google Scholar PubMed

11. Anderson DC. Sex-hormone-binding globulin. Clin Endocrinol (Oxf) 1974; 3:69–96.10.1111/j.1365-2265.1974.tb03298.xSearch in Google Scholar PubMed

12. Hammond GL. Molecular properties of corticosteroid binding globulin and the sex-steroid binding proteins. Endocr Rev 1990; 11:65–79.10.1210/edrv-11-1-65Search in Google Scholar

13. Westphal U. Steroid-protein interactions II. Monogr Endocrinol 1986; 27:198–264.10.1007/978-3-642-82486-9_7Search in Google Scholar

14. Petra PH. The plasma sex steroid binding protein (SBP or SHBG). A critical review of recent developments on the structure, molecular biology and function. J Steroid Biochem Mol Biol 1991; 40:735–53.10.1016/0960-0760(91)90299-KSearch in Google Scholar

15. Joseph DR. Structure, function, and regulation of androgen-binding protein/sex hormone-binding globulin. Vitam Horm 1994; 49:197–280.10.1016/S0083-6729(08)61148-6Search in Google Scholar

16. Vermeulen AL, Verdonck L, Van der Straeten M, Orie M. Capacity of the testosterone binding globulin in human plasma and influence of specific binding of testosterone on its metabolic clearance rate. J Clin Endocrinol Metab 1969; 29:1470–80.10.1210/jcem-29-11-1470Search in Google Scholar

17. Petra PH, Stanczyk FZ, Namkung PC, Fritz MA, Novy MJ. Direct effect of sex steroid-binding protein (SBP) of plasma on the metabolic clearance rate of testosterone in the rhesus macaque. J Steroid Biochem 1985; 22:739–46.10.1016/0022-4731(85)90280-8Search in Google Scholar

18. Plymate SR, Namkung PC, Metej LA, Petra PH. Direct effect of plasma sex hormone binding globulin (SHBG) on the metabolic clearance rate of 17β-estradiol in the primate. J Steroid Biochem 1990; 36:311–7.10.1016/0022-4731(90)90223-FSearch in Google Scholar

19. Hammes A, Andreassen TK, Spoelgen R, Raila J, Hubner N, Schulz H, et al. Role of endocytosis in cellular uptake of sex steroids. Cell 2005; 122:751–62.10.1016/j.cell.2005.06.032Search in Google Scholar

20. Burke CW, Anderson DC. Sex-hormone-binding globulin is an oestrogen amplifier. Nature 1972; 240:38–40.10.1038/240038a0Search in Google Scholar

21. Jönsson U, Malmqvist M. Real time biospecific interaction analysis, the integration of surface plasmon resonance detection, general biospecific interface chemistry and microfluidics into one analytical system. Adv Biosensors 1992; 2:291–336.Search in Google Scholar

22. Hauptmann H, Metzger J, Schnitzbauer A, Cuilleron CY, Mappus E, Luppa PB. Syntheses and ligand-binding studies of 1α- and 17α-amino-alkyl dihydrotestosterone derivatives to human sex hormone-binding globulin. Steroids 2003; 68:629–39.10.1016/S0039-128X(03)00092-8Search in Google Scholar

23. Metzger J, Schnitzbauer A, Meyer M, Söder M, Cuilleron CY, Luppa PB. Binding analysis of 1α- and 17α-dihydrotestosterone derivatives to homodimeric sex hormone-binding globulin. Biochemistry 2003; 42:13735–45.10.1021/bi035269kSearch in Google Scholar

24. Thaler M, Metzger J, Schreiegg A, Denk B, Gleixner A, Hauptmann H, et al. Immunoassay for sex hormone-binding globulin in undiluted serum is influenced by high-molecular-mass aggregates. Clin Chem 2005; 51:401–7.10.1373/clinchem.2004.034264Search in Google Scholar

25. Selby C. Sex hormone-binding globulin: origin, function and clinical significance. Ann Clin Biochem 1990; 27:532–41.10.1177/000456329002700603Search in Google Scholar

26. Kaymakoglu S, Ökten A, Cakaloglu Y, Boztas G, Besisik F, Tascioglu C, et al. Hypogonadism is not related to the etiology of liver cirrhosis. J Gastroenterol 1995; 30:745–50.10.1007/BF02349641Search in Google Scholar

27. Gravel P, Walzer C, Aubry C, Balant LP, Yersin B, Hoch-strasser DF, et al. New alterations of serum glycoproteins in alcoholic and cirrhotic patients revealed by high resolution two-dimensional gel electrophoresis. Biochem Biophys Res Commun 1996; 220:78–85.10.1006/bbrc.1996.0360Search in Google Scholar

28. Valladares L, Erices A, Lioi X, Iturriaga H. Characterization of the oligosaccharides of plasma sex hormone binding globulin from noncirrhotic alcoholic patients. Steroids 2000; 65:275–80.10.1016/S0039-128X(00)00086-6Search in Google Scholar

29. Baker HW, Burger HG, de Kretser DM, Dulmanis A, Hudson B, O'Connor S, et al. A study of the endocrine manifestations of hepatic cirrhosis. Q J Med 1976; 45:145–78.Search in Google Scholar

30. Kley HK, Nieschlag E, Wiegelmann W, Solbach HC, Krüskemper HL. Steroid hormones and their binding in plasma of male patients with fatty liver, chronic hepatitis and liver cirrhosis. Acta Endocrinol (Copenh) 1975; 72:275–85.10.1530/acta.0.0790275Search in Google Scholar

31. Gordon GG, Olivo J, Rafii F, Southren AL. Conversion of androgens to estrogens in cirrhosis of the liver. J Clin Endrocrinol Metab 1975; 40:1018–26.10.1210/jcem-40-6-1018Search in Google Scholar

32. Leowattana W. DHEAS as a new diagnostic tool. Clin Chim Acta 2004; 341:1–15.10.1016/j.cccn.2003.10.031Search in Google Scholar

33. Amory JK, Bremner W. Endocrine regulation of testicular function in men: implications for contraceptive development. Mol Cell Endocrinol 2001; 182:175–9.10.1016/S0303-7207(01)00562-7Search in Google Scholar

34. Tilbrook AJ, Clarke IJ. Negative feedback regulation of the secretion and actions of gonadotropin-releasing hormone in males. Biol Reprod 2001; 64:735–42.10.1095/biolreprod64.3.735Search in Google Scholar PubMed

Received: 2006-2-22
Accepted: 2006-5-23
Published Online: 2011-9-21
Published in Print: 2006-8-1

©2006 by Walter de Gruyter Berlin New York

Articles in the same Issue

  1. Laboratory medicine in the 2000s: programmed death or rebirth?
  2. Polymorphisms of the inflammatory system and risk of ischemic cerebrovascular events
  3. Haptoglobin polymorphism in patients with preeclampsia
  4. Fifteen polymorphisms in endothelin-1, endothelin-2 and endothelin-receptor-A genotyped by four duplex assays and seven simple assays on a LightCycler using hybridization probes
  5. Optimization of an enzymatic method for the determination of lysosomal N-acetyl-β-D-hexosaminidase and β-glucuronidase in synovial fluid
  6. An improved laboratory protocol to assess subarachnoid haemorrhage in patients with negative cranial CT scan
  7. Association of aminothiols with the clinical outcome in hemodialysis patients: comparison of chromatography and immunoassay for homocysteine determination
  8. Poor prognosis indicated by nucleated red blood cells in peripheral blood is not associated with organ failure of the liver or kidney
  9. Detection of citrate overdose in critically ill patients on citrate-anticoagulated venovenous haemofiltration: use of ionised and total/ionised calcium
  10. Unchanged androgen-binding properties of sex hormone-binding globulin in male patients with liver cirrhosis
  11. Relationship between serum uric acid, creatinine, albumin and gestational diabetes mellitus
  12. Aminothiols in human brain tumors
  13. Measurement of carnitine in hemodialysis patients – adaptation of an enzymatic photometric method for an automatic analyzer
  14. A robust liquid chromatography tandem mass spectrometry method for total plasma homocysteine determination in clinical practice
  15. Establishment of reference distributions and decision values for thyroid antibodies against thyroid peroxidase (TPOAb), thyroglobulin (TgAb) and the thyrotropin receptor (TRAb)
  16. Effects of a long-distance run on cardiac markers in healthy athletes
  17. α-Tocopherol supplementation reduces the elevated 8-hydroxy-2-deoxyguanosine blood levels induced by training in basketball players
  18. Influence of the needle bore size used for collecting venous blood samples on routine clinical chemistry testing
  19. The ratio of apoB/apoAI, apoB and lipoprotein(a) are the best predictors of stable coronary artery disease
  20. Evaluation of the analytical performance of the advanced method for cardiac troponin I for the AxSYM platform: comparison with the old method and the Access system
  21. Preliminary performance evaluation of blood gas analyzers
  22. A cost-effectiveness evaluation of reticulocyte measurement in new outpatients with or without hematologic disorders
  23. Guidelines for setting up an External Quality Assessment Scheme for blood smear interpretation. Part II: survey preparation, statistical evaluation and reporting
  24. Free light chain testing in follow-up of multiple myeloma
  25. Blood reactive oxygen metabolites (ROMs) and total antioxidant status (TAS) in patients with laryngeal squamous cell carcinoma after surgical treatment
  26. SIBioC 2006 38th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology, Turin, Italy, September 19–22, 2006
  27. Third Santorini Biologie Prospective Conference 2006: From Human Genetic Variations to Prediction of Risks and Responses to Drugs and the Environment, Santorini Island, Greece, September 29 - October 2, 2006
https://doi.org/10.1515/CCLM.2006.186
Keywords for this article
androgen metabolism; liver cirrhosis; sex hormone-binding globulin (SHBG); surface plasmon resonance biosensor

Articles in the same Issue

  1. Laboratory medicine in the 2000s: programmed death or rebirth?
  2. Polymorphisms of the inflammatory system and risk of ischemic cerebrovascular events
  3. Haptoglobin polymorphism in patients with preeclampsia
  4. Fifteen polymorphisms in endothelin-1, endothelin-2 and endothelin-receptor-A genotyped by four duplex assays and seven simple assays on a LightCycler using hybridization probes
  5. Optimization of an enzymatic method for the determination of lysosomal N-acetyl-β-D-hexosaminidase and β-glucuronidase in synovial fluid
  6. An improved laboratory protocol to assess subarachnoid haemorrhage in patients with negative cranial CT scan
  7. Association of aminothiols with the clinical outcome in hemodialysis patients: comparison of chromatography and immunoassay for homocysteine determination
  8. Poor prognosis indicated by nucleated red blood cells in peripheral blood is not associated with organ failure of the liver or kidney
  9. Detection of citrate overdose in critically ill patients on citrate-anticoagulated venovenous haemofiltration: use of ionised and total/ionised calcium
  10. Unchanged androgen-binding properties of sex hormone-binding globulin in male patients with liver cirrhosis
  11. Relationship between serum uric acid, creatinine, albumin and gestational diabetes mellitus
  12. Aminothiols in human brain tumors
  13. Measurement of carnitine in hemodialysis patients – adaptation of an enzymatic photometric method for an automatic analyzer
  14. A robust liquid chromatography tandem mass spectrometry method for total plasma homocysteine determination in clinical practice
  15. Establishment of reference distributions and decision values for thyroid antibodies against thyroid peroxidase (TPOAb), thyroglobulin (TgAb) and the thyrotropin receptor (TRAb)
  16. Effects of a long-distance run on cardiac markers in healthy athletes
  17. α-Tocopherol supplementation reduces the elevated 8-hydroxy-2-deoxyguanosine blood levels induced by training in basketball players
  18. Influence of the needle bore size used for collecting venous blood samples on routine clinical chemistry testing
  19. The ratio of apoB/apoAI, apoB and lipoprotein(a) are the best predictors of stable coronary artery disease
  20. Evaluation of the analytical performance of the advanced method for cardiac troponin I for the AxSYM platform: comparison with the old method and the Access system
  21. Preliminary performance evaluation of blood gas analyzers
  22. A cost-effectiveness evaluation of reticulocyte measurement in new outpatients with or without hematologic disorders
  23. Guidelines for setting up an External Quality Assessment Scheme for blood smear interpretation. Part II: survey preparation, statistical evaluation and reporting
  24. Free light chain testing in follow-up of multiple myeloma
  25. Blood reactive oxygen metabolites (ROMs) and total antioxidant status (TAS) in patients with laryngeal squamous cell carcinoma after surgical treatment
  26. SIBioC 2006 38th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology, Turin, Italy, September 19–22, 2006
  27. Third Santorini Biologie Prospective Conference 2006: From Human Genetic Variations to Prediction of Risks and Responses to Drugs and the Environment, Santorini Island, Greece, September 29 - October 2, 2006
Downloaded on 5.4.2026 from https://www.degruyterbrill.com/document/doi/10.1515/CCLM.2006.186/html
Scroll to top button