Sex hormones induce a gender-related difference in renal expression of a novel prostaglandin transporter, OAT-PG, influencing basal PGE ₂ concentration

Based on the nucleotide sequence of a mouse prostaglandin-specific transporter (mOAT-PG), we identified a rat homolog (rOAT-PG) which shares 80% identity with mOAT-PG in a deduced amino acid sequence. rOAT-PG transports PGE ₂ and colocalizes with 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a metabolic enzyme for PGs, in proximal tubules, suggesting that rOAT-PG is involved in PGE ₂ clearance to regulate its physiological function in the renal cortex. We found that the expression level of rOAT-PG in the renal cortex was much higher in male rats than in female rats whereas there was no gender difference in the expression level of cyclooxygenase-2, a key enzyme producing PGE ₂, and 15-PGDH in the renal cortex. Tissue PGE ₂ concentration in the renal cortex was lower in male rats than in female rats, suggesting that renocortical PGE ₂ concentration is primarily determined by the expression level of OAT-PG, which is regulated differently between male and female rats. Castration of male rat led to a remarkable reduction in OAT-PG expression and a significant increase in renocortical PGE ₂ concentration. These alterations were recovered by testosterone supplementation. These results suggest that OAT-PG is involved in local PGE ₂ clearance in the renal cortex. Although the physiological importance of the gender difference in local PGE ₂ clearance is still unclear, these findings might be a key to clarifying the physiological roles of PGE ₂ in the kidney.