Urinary Oxalate Excretion Decreased in Androgen Receptor-Knockout Mice by Suppressing Oxalate Synthesis in the Liver

Abstract

The incidence of calcium oxalate stone in men is higher than that in women. We evaluated the association between the androgen receptor (AR) and urinary oxalate excretion using Crefloxed male androgen receptor-knockout (ARKO) mice (AR L-/Y ) and floxed mice (AR L+/Y ) as control. Four-teen-week-old AR L-/Y and AR L+/Y mice were fed distilled water. Drinking water was then swapped for 0.5% ethylene glycol (EG). Urinary oxalate was measured on days 0, 14, and 28. Urinary calcium, inorganic phosphorus, citrate, uric acid, and ion-actibity products of calcium oxalate (APCaOx) in mouse, AP (CaOx)-indexMOUSE, were evaluated on days 0 and 15. On day 28, livers were harvested to measure mRNA expression of enzymes. Urinary oxalate excretion was significantly higher in AR L+/Y than in AR L-/Y mice 14 and 28 days after EG treatment (p < 0.05). Since AR L-/Y mice exhibited atrophic testes and low serum testosterone, both ARKO and control mice were orchiectomized and implanted DHT pellets (AR L-/Y -ORX-DHT, and AR L+/Y -ORX-DHT), and the same experiments as above were performed. EG loading for 14 and 28 days resulted in significantly higher excretion in AR L+/Y -ORX-DHT mice than AR L-/Y -ORX-DHT mice (p < 0.005). AP(CaOx)-indexMOUSE was significantly higher in ARL+/Y-ORX-DHT mice than in AR L-1/Y -ORX-DHT mice. mRNA expression levels of glycolate oxidase (GO) in liver were lower in ARKO mice than in control ones. AR modulates the excretion of oxalate in urine after EG treatment, which may be associated with increased oxalate synthesis by activated GO in the liver via the AR pathway.