Tissue distribution of estradiol 17-sulfate 2- and 4-hydroxylation enzymes in the rat.
The activities of 2- and 4-hydroxylation enzymes of estradiol 17-sulfate in various rat tissues were measured by determining 2-hydroxyestradiol 17-sulfate and 4-hydroxyestradiol 17-sulfate by high performance liquid chromatography equipped with an electrochemical detector. Incubations were carried out in the presence of a nicotinamide adenine dinucleotide phosphate (NADPH)-generating system using microsomal fractions of each tissue. The livers of male and female rats, followed by the kidneys, had the highest 2-hydroxylase activities, while other tissues, including the brain, heart, lung, testis, ovary and uterus, possessed similar levels of activity. With regard to 4-hydroxylase, again the liver, followed by the ovary, had the highest activity. There was no significant difference in the activities of other tissues investigated. In addition, two catechol estrogens, 6 beta-, 7 beta- and 16 alpha-hydroxylated metabolites of estradiol 17-sulfate, were formed when male heart and lung and female liver and kidney were used. Male kidney was found to have a weak 6 beta-hydroxylase activity, also. These results show that various rat tissues, including the liver, have 2- and 4-hydroxylase activities for estradiol 17-sulfate and that some of the tissues have additional metabolic abilities such as hydroxylation at 6 beta-, 7 beta- or 16 alpha-positions of the substrate.
Watanabe
K
K
Hokkaido Institute of Pharmaceutical Sciences, Otaru, Japan.
Yoshizawa
I
I
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D002851:Chromatography, High Pressure Liquid; D065633:Cytochrome P-450 CYP1B1; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D008297:Male; D009249:NADP / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013250:Steroid Hydroxylases / Q000378:metabolism*; D014018:Tissue Distribution
C031555:estradiol sulfate; C048615:estradiol 17-sulfate; D004958:Estradiol; D009249:NADP; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C585499:Cyp1b1 protein, rat; D065633:Cytochrome P-450 CYP1B1