Age, gender and region-specific differences in drug metabolising enzymes in rat ocular tissues.

Previously we have reported our analyses of cytochrome P450 (CYP) expression in rat ocular tissues and in our current study we have extended these analyses to the different stages of growth in both male and female rats. Additionally, we have examined the expression levels of the different conjugation enzymes, sulfotransferases (SULTs), UDP-glucuronosyl transferases (UGTs) and glutathione S-transferases (GSTs), in ocular tissues. In 5-week-old animals, the CYP genes, CYP2B2 and CYP3A1, were abundantly expressed in the lens, with higher CYP1A1 expression detectable in the extra-lenticular tissues, of both genders. However, the expression of CYP1A2 and CYP2E1 in female ocular tissues was more extensive than in male. Moreover, in females the expression of the phenol-sulfating SULTs, ST1A1, ST1B1 and ST1C1, was more abundant in the extra-lenticular tissues, whereas the levels of the hydroxysteroid-sulfating SULTs, ST2A1 and ST2A5, predominated in the lens. The expression levels of the UGTs, UGT1A1, UGT1A6 and UGT2B1, were also higher in the female extra-lenticular tissues but the expression of the GSTA subfamily (GSTA1 and GSTA2) was very weak in the ocular tissues of both genders. The overall gene expression profiles were found to change with the age of the animals (from 3 to 8 weeks) and, in general, the expression levels of the CYPs and SULTs declined with age, whereas the levels of the UGTs and GSTs increased. These results demonstrate that the expression profiles of drug metabolising enzymes show both region- and gender-specific patterns in rat ocular tissues.