Influence of Sex Differences on the Renal Secretion of Organic Anions

Abstract

The kidney's responsiveness to male sexual hormones has been often neglected. Renal secretion of organic anions is higher in male than in female individuals; as a consequence, most of the xenobiotics that are excreted from the organism through this pathway are eliminated more rapidly by males than by female animals. To gain further insight into this issue, we studied in vitro and in vivo characteristics of the transport of p-aminohippurate (PAH), a suitable marker for this system, in male and female rats, under different hormonal conditions. Kinetics of PAH showed a shorter elimination half-time in male than in female rats (t(1/2el): male = 16.2 +/- 2.1 min, female = 25.7 +/- 4.5 min, P < 0.05). Castration of male rats increased t(1/2el) to a value similar to that of female rats (t(1/2el): orchiectomized rat = 28.1 +/- 7.1 min). Testosterone treatment of female rats increased the elimination rate to a value similar to that of male rats. In vitro PAH uptake by renal cortical slices from intact male rats was higher than that by slices from orchiectomized rats. Kinetic analyses of PAH uptake suggest that the difference was caused by a lower number of transporting molecules in orchiectomized than in intact animals, whereas the transporting capacity for each carrier was similar in male and in orchiectomized rats. Our results suggest that testosterone increases the number of functional carriers for PAH in the kidney.

Gender-Specific and Developmental Influences on the Expression of Rat Organic Anion Transporters

“…Furthermore, renal Oat1 mRNA expression in male rats tended to be higher than in females. This trend paralleled data reported by Reyes et al (1998) that identified more active PAH transport in male rat renal cortical slices when compared with female slices. Noting that the Oat1 mRNA expression was principally in kidney in this study (Fig.…”

“…Furthermore, age and gender are known to influence pharmacokinetic parameters, such as clearance and half-life of many drugs, as well as the extent of and sensitivity to drug toxicity. Reyes et al (1998) demonstrated a gender difference in renal transport in which male rats transported more PAH than did females. Moreover, PAH half-life was extended in castrated male rats as compared with intact males.…”

Low-dose indomethacin after ischemic acute kidney injury prevents downregulation of Oat1/3 and improves renal outcome

“…With respect to long-term regulation of renal organic anion transport, much less data are available. There is evidence that renal organic anion transport is regulated by sex steroids (27), which is now shown to be most probably due to regulation of Oat1 and Oat3 (4,22). Moreover, hyperuricemia was shown to reversibly downregulate Oat1 and Oat3 (14,15).…”

Prostaglandin E2 Inhibits Its Own Renal Transport by Downregulation of Organic Anion Transporters rOAT1 and rOAT3

“…With respect to long-term regulation of renal organic anion transport, fewer data are available. There is evidence that renal organic anion transport is regulated by sex steroids (10), which now is shown to be most probably due to regulation of OAT1 and OAT3 (11,12) and maybe OAT2 (12). Moreover, hyperuricemia was shown to reversibly downregulate OAT1 and OAT3 (13) in rats.…”