Summary
Presystemic sulphation and glucuronidation at OH-C17 limits the bioavailability of testosterone; the aim of this investigation was to describe the variability in testosterone sulphation and glucuronidation rates in the human liver. Liver samples were obtained from 61 women and 40 men of similar age (mean 53 and 55 yers, respectively) submitted to surgery. The mean rate of testosterone sulphation was significantly (P=0.002) higher in men (22.4 pmol/min/mg) than in women (17.5 pmol/min/mg), was not age-dependent, followed bimodal distribution and varied over 7-fold in men and women. There was a weak, but significant negative correlation (r=−0.380;P=0.003), between the rate of testosterone glucuronidation and age in the liver of women but not in that of men. The mean rate (pmol/min/mg) of testosterone glucuronidation was 155 (men) and 105 (women) (NS) and varied over 20-fold. When the rate of testosterone glucuronidation was expressed on the basis of g liver equivalent, the mean estimates were significantly (P=0.003) greater in men (3323 pmol/min/g) than in women (1841 pmol/min/g). The present findings are consistent with the view that the hepatic activities of sulphotransferase and glucuronosyltransferase are higher in men than in women and that they vary in the human liver.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Sherins R.J., Winters S.J. (1978): Management of disorders of the testis. In: Melmon K.L., Morrelli H.F. (Eds) Clinical Pharmacology, 2nd edn. New York: Macmillan, 579–591.
Wilson J.D. (1996): Androgens. In: Hardman J.G., Limbrid L.E., Molinoff P.B., Ruddon, R.W., Goodman Gilman A. (Eds) Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 9th edn. New York: McGraw-Hill, 1441–1457.
Temellini A., Giuliani L., Pacifici G.M. (1991): Interindividual variability in the glucuronidation and sulphation of ethinyloestradiol in human liver. Br. J. Clin. Pharmacol., 31, 661–664.
Romiti P., Giuliani L., Pacifici G.M. (1992): Interindividual variability in the N-sulphation of desipramine in human liver and platelets. Br. J. Clin. Pharmacol., 33 17–23.
Pacifici G.M., Temellini A., Castiglioni M., D’Alessandro C., Ducci A., Giuliani L. (1994): Interindividual variability of the human hepatic sulphotransferases. Chem. Biol. Interact., 92, 219–231.
Pacifici G.M., Bigotti R., Marchi G., Giuliani L. (1993): Minoxidil sulphation in human liver and platelets. A study of interindividual variability. Eur. J. Clin. Pharmacol., 45, 337–341.
Pacifici G.M., Giulianetti B., Quilici M.C. et al. (1997): (−)-Salbutamol sulphation in the human liver and duodenal mucosa: interindividual variability. Xenobiotica, 27, 279–286.
Pacifici G.M., Ferroni M.A., Temellini A., Gucci A., Morelli M.C., Giuliani L. (1994) Human liver budesonide sulphotransferase is inhibited by testosterone and correlates with testosterone sulphotransferase. Eur. J. Clin. Pharmacol., 46, 49–54.
Pacifici G.M., Evangelisti L., Giuliani L., Metelli R.M., Giordani R. (1996): Zidovudine glucuronidation in human liver: interindividual variability. Int. J. Clin. Pharmacol. Ther., 43: 329–334.
Singer S.S. (1978): Enzymatic sulphation of steroids. Biochim. Biophys. Acta, 539, 19–30.
Rao G.S., Haueter G., Rao M.L., Breuer H. (1976): An improved assay for steroid glucuronyltransferase in rat liver microsomes. Anal. Biochem., 74, 35–40.
Foldes A., Meek J.K. (1973): Rat brain phenol sulphotransferase partial purification and some properties. Biochim. Biophys. Acta, 327, 365–374.
Anderson, R.J., Weinshilboum R.M. (1980): Phenolsulphotransferase in human tissues: radiochemical enzymatic assay and biochemical properties. Clin. Chim. Acta, 193, 79–90.
Cappiello M., Giuliani L., Pacifici G.M. (1990): Differential distribution of phenol and catechol sulphotransferases in human liver and intestinal mucosa. Pharmacology, 40, 69–76.
Pacifici G.M., Back D.J. (1988): Sulphation and glucuronidation of ethinyloestradiol in human liver in vitro. J. Steroid Biochem., 31, 345–349.
Lowry O.H., Rosebrough N.J., Farr A., Randall R.J. (1951): Protein measurement with Folin phenol reagent. J. Biol. Chem., 193, 265–275.
Burchell B., Brierley C.H., Rance D. (1995): Specificity of human UDP-glucuronosyltransferases and xenobiotic glucuronidation. Life Sci., 57, 1819–1831.
Yue Q.Y., Svensson J-O., Alan C., Sjoqvist F., Sawe J. (1989): Interindividual and interethnic differences in the demethylation and glucuronidation of codeine. Br. J. Clin. Pharmacol., 28, 629–637.
Bock K.W., Scherenk D., Foster A. et al. (1994): The influence of the environmental and genetic factors on CYP2D6, CYP1A2 and UDP-glucuronosyltransferase in man using sparteine, caffeine and paracetamol as probes. Pharmacogenetics, 4: 209–218.
Vincent-Viry W., Cossy C., Gaiteau M.M. et al. (1995): Lack of genetic polymorphism in the glucuronidation of fenofibric acid. Pharmacogenetics, 5, 50–52.
Patel M., Tang B.K., Grant D.M., Kalow W. (1995): Interindividual variability in the glucuronidation of (S)-oxazepam contrasted with that of (R)-oxazepam. Pharmacogenetics, 5, 287–297.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pacifici, G.M., Gucci, A. & Giuliani, L. Testosterone sulphation and glucuronidation in the human liver: interindividual variability. European Journal of Drug Metabolism and Pharmacokinetics 22, 253–258 (1997). https://doi.org/10.1007/BF03189815
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF03189815