Short-term effects of tamoxifen, medroxyprogesterone acetate, and their combination on receptor kinetics and 17 beta-hydroxysteroid dehydrogenase in human endometrium.
The interactions of an antiestrogen (tamoxifen) and a progestin (medroxyprogesterone acetate) on endometrial 17 beta-hydroxysteroid dehydrogenase activities were studied in short-term experiments (four to 96 hours) in normally menstruating women at the follicular phase and were related to simultaneously measured concentrations of cytosol and nuclear estrogen and progestin receptors. Tamoxifen effected a decrease in the activity of 17 beta-hydroxysteroid dehydrogenase. This was associated with an apparent translocation to and retention of estrogen receptor in the nucleus without any significant changes in cellular progestin receptor. Medroxyprogesterone acetate administration led to a rapid increase in endometrial 17 beta-hydroxysteroid dehydrogenase activity, and depletion of cytosol and total cellular progestin receptor. Combination of the drugs led to effects that could be addressed to the individual drugs separately, and under the experimental conditions the effects of medroxyprogesterone acetate were uninfluenced by simultaneous tamoxifen administration. Put together with the authors' previous findings on the same parameters during long-term (three-week) medroxyprogesterone acetate administration, it seems possible that potentiation of progestin effects on endometrial carcinoma is not to be expected during long-term simultaneous antiestrogen-progestin treatment. It is therefore likely that the favorable effects of combining these two drugs in long-term treatment are due to their different endocrine action mechanisms.
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000328:Adult; D003600:Cytosol / Q000378:metabolism; D004347:Drug Interactions; D004717:Endometrium / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D006801:Humans; D007700:Kinetics; D008525:Medroxyprogesterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate; D008598:Menstruation; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000187:drug effects* / Q000378:metabolism; D013268:Stimulation, Chemical; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D017258:Medroxyprogesterone Acetate; D015067:17-Hydroxysteroid Dehydrogenases; C032690:3-alpha-(17-beta)-hydroxysteroid dehydrogenase (NAD(+)); D008525:Medroxyprogesterone