TY - JOUR
T1 - Sex hormones induce a gender-related difference in renal expression of a novel prostaglandin transporter, OAT-PG, influencing basal PGE 2 concentration
AU - Hatano, Ryo
AU - Onoe, Kimitaka
AU - Obara, Masaya
AU - Matsubara, Mitsunobu
AU - Kanai, Yoshikatsu
AU - Muto, Shigeaki
AU - Asano, Shinji
PY - 2012/2
Y1 - 2012/2
N2 - 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.
AB - 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.
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U2 - 10.1152/ajprenal.00366.2011
DO - 10.1152/ajprenal.00366.2011
M3 - Article
C2 - 22031854
AN - SCOPUS:84856204828
VL - 302
SP - F342-F349
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
SN - 1931-857X
IS - 3
ER -