Differential expression of 17 beta-hydroxysteroid dehydrogenases types 2 and 4 in human endometrial epithelial cell lines

In the endometrium two enzymes are known to convert estradiol to its inacti ve metabolite estrone: microsomal 17 beta-hydroxysteroid dehydrogenase type 2 (17 beta-HSD2) and peroxisomal 17 beta-HSD4. In order to elucidate the p articular function of each of these two different enzymes, the human endome trial epithelial cell lines HEC-1-A and RL95-2 were examined with respect t o the expression of 17 beta-HSD isozymes. They were compared with human end ometrium in vivo. Non-radioactive in situ hybridization revealed both enzym es in glandular epithelial cells of human endometrium. The two cell lines w ere screened for mRNA expression of 17 beta-HSD 1-4 by RT-PCR and Northern blot. 17 beta-HSD2 and 4 could be detected by either method, 17 beta-HSD1 o nly by RT-PCR, 17 beta-HSD3 not at all. Both cell lines were proven to have no receptor for progesterone which is known as a physiological inducer of several 17 beta-HSD isozymes. To study the regulation of 17 beta-HSD2 and 1 7 beta-HSD4, the concentration of fetal calf serum in the cell culture medi a was reduced stepwise to 0.3% by dilution with a defined serum replacement . This treatment led to an inhibition of 17 beta-HSD2 mRNA expression and a n increase in the mRNA expression of 17 beta-HSD4. Concomitantly, distinct morphological changes were observed, such as a decrease in the number and l ength of microvilli and a decrease in the formation of domes on top of the monolayers. The endometrial epithelial cell lines HEC-1-A and RL95-2 repres ent a suitable in vitro model for further studies of the differential expre ssion of the major endometrial HSD isozymes, independent of the effect of p rogesterone.