Genetic variability, the urinary testosterone/ epitestosterone ratio and anabolic steroids abuse

Project Title: Genetic variability, the urinary testosterone/epitestosterone ratio and anabolic steroid abuse

Researchers: M. Finel (University of Helsinki, Finland), T. Kuurane (United Laboratory Ltd., Finland)

Year accepted: 2006

Summary: The main conclusions of our studies within this WADA supported project are the following:

1. Examination of all the 19 human UGTs of subfamilies 1A, 2A and 2B revealed that UGT2B17 is by far the main contributor to testosterone glucuronidation in man. This result provides the explanation for the previously observed effect of UGT2B17 deletion on the T/E.

2. Examination of all the 19 human UGTs of subfamilies 1A, 2A and 2B revealed that UGT2B7 is by far the main contributor to epitestosterone glucuronidation in man.

3. Both UGT2B7 and UGT2B17 are the major contributors to the glucuronidation of androsterone as well as etiocholanolone, even if UGT2B17 has significantly higher affinity and higher turnover rate with etiocholanolone.

4. UGT2B7 is the main contributor to the glucuronidation of 5α-diol on the 3-OH, whereas UGT2B15 and UGT2B17 are mainly responsible for its glucuronidation on the 17-OH.

5. UGT2B17 is the main contributor to the glucuronidation of 5β-diol, primarily on the 17-OH.

6. UGT2A1 has the capacity for glucuronidating testosterone, epitestosterone, and etiocholanolone at high rate, but it probably does not contribute noticeably to the level of androgen glucuronides in the urine due to its limited expression.

7. Low levels of urinary testosterone glucuronide concentration are not compensated for by higher level of testosterone sulfate.

8. Low levels of urinary epitestosterone glucuronide, not high levels of testosterone glucuronide, are the main reason for high T/E in athletes that have not used exogenous testosterone.

9. In an effort to develop a system for detecting possible abuse of exogenous testosterone by sportsmen that will not be dependent on the activity of UGT2B17, we suggest to concentrate on 3-glucuronide of 5α-diol. Another possible target molecule from this point of view is androsterone glucuronide.