Effect of progestins, estradiol, and coenzymes NAD and NADPH on the interconversion of estradiol and estrone in rabbit uterus in vitro

The biotransformation of estradiol (E2) and estrone (E1) in the uterus of rabbits treated with norgestrel (NG), norethindrone (NET), norethindrone acetate (NETA), progesterone (P4), and E2 either by subcutaneous injection in oil or by intrauterine steroid-releasing silastic implants was carried out under an in vitro short-term incubation system. The studies have shown that E2 stimulates 17 beta-hydroxysteroid dehydrogenase (17 beta-OHSD) much more than P4 as compared to untreated controls. The kinetic studies on E2 metabolism in the presence of added coenzyme NAD showed an initial rapid estrone formation and a gradual reconversion of E1 to E2. The addition of NADPH, ATP, and glucose-6-phosphate facilitates the reconversion of E1 to E2. The interconversion of E2 and estrone in the presence of coenzymes was five- to ten-fold higher in the endometrium than in the myometrium per milligram protein. Both E2 and progestins stimulate the uterine 17 beta-OHSD activity in rabbit uterus. This study further suggested that the hormone-induced metabolism of estradiol and estrone in the rabbit uterus is essentially modulated by the availability of coenzymes.