Organic anion transporting polypeptides (OATP/SLCO) 2B1 and 1B3 mediate the cellular influx of androgens.
Very few studies have specifically evaluated genetic variation and androgen transport. The aim of this study was to
evaluate if human genetic variation in SLCO2B1 and SLCO1B3 genes are associated with the disposition of testosterone
and five of its metabolites before and two days after the administration of a single intramuscular dose (500 mg) of
testosterone enanthate in healthy volunteers (N=43). Serum concentration of testosterone and its metabolites were
determined by GCMS/LCMS. Two functional polymorphisms in SLCO2B1 (rs12422149) and SLCO1B3 (rs4149117)
genes were characterized by allelic discrimination. These SNPs have been hitherto shown to markedly affect the cellular
uptake of hormones and hence, they were selected. Individuals homozygous for the SLCO2B1 G-allele displayed lower
levels of total testosterone prior to (5.09 ng/ml) and two days after (13.58 ng/ml) testosterone injection, as compared to
individuals expressing the A-allele (6.01 ng/ml and 21.88 ng/ml, respectively) (p=0.05 and p=0.002, respectively).
Moreover, the concentration of the testosterone metabolites (dihydrotestosterone (DHT), androsterone, 5α-androstane-
3α,17β-diol-17-glucuronide) were significantly lower in subjects with GG genotype at 48 hours post-dose. Individuals
homozygous for the SLCO2B1 G allele had a smaller increase in serum testosterone and DHT levels (0.03-fold/kg and
0.02-fold/kg) compared to carriers of the A allele (0.05-fold/kg and 0.03-fold/kg) (p=0.04 and p=0.02, respectively). The
SLCO1B3 polymorphism did not show any significant association with serum testosterone levels or the other androgens
metabolites investigated. In conclusion, here we report, for the first time to the best of our knowledge, that genetic
variation in SLCO2B1 gene impacts the systemic concentrations of testosterone and some of its metabolites, after
administration of a single-dose testosterone enanthate. These data also serve as a foundation to examine in the future the
role of human genetic variation in SLCO2B1 in relation to testosterone pharmacokinetics, particularly in the context of
sports medicine and doping testing or clinical use as a replacement therapy.