Abstract
The incidence of calcium oxalate stone in men is higher than that in women. We evaluated the as- sociation between the androgen receptor (AR) and urinary oxalate excretion using Cre-floxed male androgen receptor-knockout (ARKO) mice (ARL−/Y) and floxed mice (ARL+/Y) as control. Four- teen-week-old ARL−/Y and ARL+/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 cal- cium, inorganic phosphorus, citrate, uric acid, and ion-actibity products of calcium oxalate (AP- CaOx) 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 orchiec- tomized and implanted DHT pellets (ARL−/Y-ORX-DHT, and ARL+/Y-ORX-DHT), and the same expe- riments 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 ARL−/Y-ORX-DHT mice. mRNA expression le- vels 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 oxa- late synthesis by activated GO in the liver via the AR pathway. * Corresponding author.
Highlights
The incidence of idiopathic calcium oxalate (CaOx) renal stone disease in men is 2.5 - 3 times higher than that in women [1] [2]
To assess how androgen receptor (AR) is related to oxalate metabolisms, we evaluated urinary oxalate levels and the expression of hepatic glycolate oxidase (GO) and AGT mRNA during ethylene glycol (EG) loading in androgen receptor-knockout (ARKO) mice
We measured levels of urinary oxalate in the ARL+/Y and ARL−/Y mice fed normal diet and water, and found that urinary oxalate excretion was higher in the ARL+/Y mice compared with that in ARL−/Y mice, and treatment with EG exacerbated this difference
Summary
The incidence of idiopathic calcium oxalate (CaOx) renal stone disease in men is 2.5 - 3 times higher than that in women [1] [2]. The reason for the gender disparity remains unclear, the several studies have demonstrated that urinary excretion of calcium, oxalate, and uric acid is higher, and that of citrate is lower, in males than in females [3] [4]. Among these substances, urinary oxalate is a strong dicarboxylic organic acid that forms insoluble salt with calcium, and is one of the most important factors in calcium oxalate kidney stone formation [5] [6]. Glyoxylate is metabolized to glycine by serine pyruvate aminotransferase/alanine: glyoxylate amino transferase (SPT/AGT), which is thought to inhibit oxalate synthesis [12]
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