Regulation of estrogen receptor alpha and progesterone receptor (isoform Aand B) expression in cultured human endometrial cells

The effects of RU 486 together with estradiol and progesterone on estrogen receptor alpha and progesterone receptor (isoforms A and B) expression were studied in human endometrial long term cultures at the mRNA and protein le vel. We asked whether ligand induced receptor regulation. found in mammals in vivo, is also found in human cultured endometrial cells with special reg ard to the progesterone isoforms A and B. Endometrial cultures were maintai ned for 27 days. Media were supplemented with progesterone and/or estradiol alone or in combination with RU 486. Receptor expression (estrogen recepto r alpha and progesterone receptor isoform A and B) was examined at the mRNA level by RT-PCR and at the protein Level by western blot analysis. All rec eptor types examined were expressed in our culture model. Estradiol led to a general increase of receptor expression whereas treatment with estradiol in combination with progesterone down regulated receptor expression. The re ceptor down regulation was not found when RU 486 was additionally supplemen ted into the medium. Activation or inhibition of expression due to these tr eatments was similar for both PR isoforms. Our results(1) show that in our culture system estradiol induced up regulation of estrogen receptor and pro gesterone receptor A and B and suggest that the estrogen induced up regulat ion is prevented by progesterone (2) a clear cut antigestagenic effect of R U 486 and (3) suggest that both progesterone isoforms are analogously regul ated in our culture model. We conclude that human endometrial cell cultures are suitable for the study of the dynamics of steroid receptor expression.