Major glucuronide metabolites of testosterone are primarily transported by MRP2 and MRP3 in human liver, intestine and kidney
Cindy Yanfei Li; Abdul Basit; Anshul Gupta; Zsuzsanna Gáborik; Emese Kis; Bhagwat Prasad
The Journal of Steroid Biochemistry and Molecular Biology2019
Summary (paraphrased)
The authors quantified how the four major testosterone glucuronides (testosterone glucuronide, DHT glucuronide, androsterone glucuronide, etiocholanolone glucuronide) are cleared from human liver, intestine, and kidney. Using recombinant transporter vesicles plus quantitative proteomics, they showed MRP2 and MRP3 are the dominant efflux transporters, with MRP2 preferentially handling the glucuronides of active androgens and MRP3 those of inactive ones. Because these glucuronides are excreted into bile, they reach the gut lumen where they can be deconjugated back to active androgen, implicating transporter-driven biliary efflux as a control point for enterohepatic recirculation of androgens.
Why it’s in the systems review
Powers' model hinges on how much androgen is actually eliminated versus trapped or recycled, yet clearance is usually discussed only at the UGT-conjugation step. This study fills the missing next step: the transporters that move androgen glucuronides into bile, which is the direct precondition for gut deconjugation and reabsorption. It belongs in the causal-pathway search as the mechanistic bridge between glucuronidation and enterohepatic androgen recycling.