Читать книгу Drug Transporters - Группа авторов - Страница 95

Expression of Mate transporters can vary by sex and age. Within the kidneys of rats, rMate1 and rMate2‐K mRNA begin to be expressed at postnatal days 21 and 1, respectively, and peak at 6 months of age before declining with advanced age [75]. Interestingly, older rats (~18 months) have heightened susceptibility to the nephrotoxicity of the Mate1 substrate, cisplatin [76]. This increased susceptibility is likely due to the reduced expression of Mate1 protein as expression of other cisplatin transporters were unchanged in 18‐month‐old rats [76].

Sex differences in Mate transporters have been observed in mice, but not in humans, and may reflect differential regulation by hormones across species. Expression of mMate1 mRNA is slightly higher in the livers of female mice compared with males. However, within female kidneys, mMate1 mRNA levels are lower than that observed in male mice [14]. Interestingly, expression of mMate2 mRNA in the kidneys can be reduced by removal of the ovaries in female mice [77]; supplementation with 17ß‐estradiol restores mMate2 expression. By comparison, there is no change in mMate1 mRNA in ovariectomized mice. Treatment of mice with testosterone for 7 days increases the protein expression of mMate1 and mMate2 [78]. These findings provide initial insights into the hormonal regulation of Mate transporters in mice.