Sex hormones induce a gender-related difference in renal expression of a novel prostaglandin transporter, OAT-PG, influencing basal PGE2concentration

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Abstract
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 PGE2and colocalizes with 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a metabolic enzyme for PGs, in proximal tubules, suggesting that rOAT-PG is involved in PGE2clearance 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 PGE2, and 15-PGDH in the renal cortex. Tissue PGE2concentration in the renal cortex was lower in male rats than in female rats, suggesting that renocortical PGE2concentration 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 PGE2concentration. These alterations were recovered by testosterone supplementation. These results suggest that OAT-PG is involved in local PGE2clearance in the renal cortex. Although the physiological importance of the gender difference in local PGE2clearance is still unclear, these findings might be a key to clarifying the physiological roles of PGE2in the kidney.

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