Effect of tamoxifen, estradiol 17 beta on coenzymes NAD, NADPH and the metabolism of estradiol and estrone in rabbit uterus in vivo.
Biotransformation of estradiol (E2) and estrone (E1) and the concentrations of NAD, NADPH and 17 beta-estradiol dehydrogenase (E2DH) were measured in the uterus of rabbits treated with tamoxifen (Tam) in two doses; 100 micrograms/day, (Tam 100) and 500 micrograms/day, (Tam 500), E2 (10 micrograms/day) and combination of E2 + Tam 500 for 4 days. The concentration of NAD in Tam 500 treated group was significantly higher than E2, low dose Tam and E2 + Tam 500 treated groups (P < 0.01). The concentration of NAD in E2+ Tam 500 uteri was also significantly higher than E2 treated uteri. The concentration of NADPH was not significantly different from each other amongst the various treatment groups. The studies have shown that E2DH in E2 treated uteri was less than control and Tam 500 treated groups. A significant rise in the enzyme estradiol oxidoreductase (E2OR) activity (P < 0.02) was observed in E2 + Tam 500 treated uteri over control and other treated groups whereas high dose Tam decreased the E2OR activity significantly over the E2 treated group. The rate of conversion of E1 to E2 in Tam 500 treated group was significantly less than the other treatment groups except E2 + Tam 500 treated group (P < 0.04). This study showed that E2 decreases the uterine biosynthesis of NAD and E2DH and the biotransformation of E2 to E1, while high dose Tam increases uterine NAD, E2DH activity and E2 to E1 conversion.
Bhargava
S
S
Department of Reproductive Biology, All India Institute of Medical Sciences, New Delhi.
Murugesan
K
K
Vij
U
U
Farooq
A
A
D000818:Animals; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D004960:Estradiol Dehydrogenases / Q000378:metabolism; D004970:Estrone / Q000378:metabolism; D005260:Female; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D011817:Rabbits; D013629:Tamoxifen / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D013629:Tamoxifen; D009243:NAD; D004970:Estrone; D004958:Estradiol; D009249:NADP; D004960:Estradiol Dehydrogenases