17-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-2 - CHROMOSOMAL ASSIGNMENT AND PROGESTIN REGULATION OF GENE-EXPRESSION IN HUMAN ENDOMETRIUM

The cDNAs for two separate human 17 beta-hydroxysteroid dehydrogenases (17 beta-HSD) have been isolated and sequenced. The well-studied huma n placental cytosolic 17 beta-HSD (also referred to as estradiol dehyd rogenase) preferentially catalyzes the reduction of estrone to estradi ol-17 beta and the reduction of the C-20-ketone of progesterone to 20 alpha-dihydroprogesterone. This isoform of the enzyme has been referre d to as 17 beta-HSD type 1 and localized to chromosome 17. A second 17 beta-HSD isoform (referred to as type 2) is localized in the endoplas mic reticulum of human trophoblast and is characterized by the prefere ntial oxidation of the C-17 beta-hydroxyl group of C-18- and C-19-ster oids and the C-20 alpha-hydroxyl group of 20 alpha-dihydroprogesterone . In this study, we determined the chromosomal localization of human 1 7 beta-HSD type 2, the expression of this gene in human endometrium, a nd the tissue distribution of the mRNA. We found that the human 17 bet a-HSD type 2 gene is localized on chromosome 16, 16q24. 17 beta-HSD ty pe 2 mRNA (similar to 1.5 kb) was identified in human endometrial tiss ues by Northern analysis of total RNA (10 mu g). The highest levels of 17 beta-HSD type 2 mRNA were found in endometrial tissues obtained du ring the mid- to late secretory phase of the ovarian cycle (i.e., duri ng the time of high plasma levels of progesterone). 17 beta-HSD type 2 mRNA levels were much greater in glandular epithelium than in the str omal cells isolated from secretory phase endometrium. The levels of 17 beta-HSD type 2 mRNA in secretory phase endometrium were approximatel y one-tenth that in villous trophoblast tissue from human placenta. We did not detect 17 beta-HSD type 1 mRNA in endometrial tissue by North ern analysis of total (10 mu g) RNA. These findings are consistent wit h the view that the progestin-regulated 17 beta-HSD of the glandular e pithelium of the human endometrium is primarily, if not exclusively, t he product of the 17 beta-HSD type 2 gene. 17 beta-HSD type 2 mRNA was present in human placenta, liver, and small intestine; much smaller a mounts, barely detectable by Northern analysis of poly(A)(+) RNA, were present in prostate, kidney, pancreas, and colon, but not in heart, b rain, skeletal muscle, spleen, thymus, ovary, or testis.