To study the disposition of serum testosterone
and seven of its metabolites before and after 2 days of an intramuscular dose (500 mg) of testosterone
enanthate in relation to the phosphodiesterase
(PDE7B) and the uridine 5′-diphospho-glucuronosyltransferase
Patients were genotyped for UGT2B17 deletion polymorphism and single nucleotide polymorphisms in the PDE7B
gene. The involvement of PDE7B in hydrolysis of enanthate was assessed in human liver homogenates.
Genetic variation in the PDE7B
gene was found to be associated with the serum level of testosterone
. Individuals homozygous for PDE7B
rs7774640 G allele had a smaller increase (2.5-fold) in the serum testosterone
levels compared with carriers of the A allele (3.9-fold, P
=0.0006). In addition, genetic variation in the PDE7B
gene significantly influences the testosterone
/epitestosterone ratio, a biomarker of testosterone
doping. Our in-vitro incubation studies confirmed that PDE7B serves as a catalyst of the hydrolysis of testosterone
enanthate. The UGT2B17 deletion polymorphism did not show any significant association with serum testosterone
levels or the other androgen metabolites investigated.
We have shown that PDE7B is involved in the hydrolysis of testosterone
enanthate and that genetic variation in the PDE7B
gene is a determinant of the systemic levels of testosterone
after administration of testosterone
enanthate. It is reasonable to believe that the genetic variation in testosterone
bioavailability may be correlated to varying effects of this androgen, whether it is used for replacement therapy or abused in doping. Thus our results may be important to consider in doping test programmes and in therapeutics with androgens and other esterified drugs.