Rapid Publication 17 f 8 - Hydroxysteroid Dehydrogenase Type 2 : Chromosomal Assignment and Progestin Regulation of Gene Expression in Human Endometrium

The cDNAs for two separate human 17,B-hydroxysteroid dehydrogenases (17p-HSD) have been isolated and sequenced. The well-studied human placental cytosolic 17wBHSD (also referred to as estradiol dehydrogenase) preferentially catalyzes the reduction of estrone to estradiol-17/3 and the reduction of the C-20-ketone of progesterone to 20dihydroprogesterone. This isoform of the enzyme has been referred to as 17j8-HSD type 1 and localized to chromosome 17. A second 17fi-HSD isoform (referred to as type 2) is localized in the endoplasmic reticulum of human trophoblast and is characterized by the preferential oxidation of the C-17fi-hydroxyl group of C18and C19-steroids and the C-20a-hydroxyl group of 20a-dihydroprogesterone. In this study, we determined the chromosomal localization of human 1713-HSD type 2, the expression of this gene in human endometrium, and the tissue distribution of the mRNA. We found that the human 17,B-HSD type 2 gene is localized on chromosome 16, 16q24. 17/8-HSD type 2 mRNA ( 1.5 kb) was identified in human endometrial tissues by Northern analysis of total RNA (10 ,ug). The highest levels of 17.3HSD type 2 mRNA were found in endometrial tissues obtained during the midto late secretory phase of the ovarian cycle (i.e., during the time of high plasma levels of progesterone). 17fi-HSD type 2 mRNA levels were much greater in glandular epithelium than in the stromal cells isolated from secretory phase endometrium. The levels of 17fi-HSD type 2 mRNA in secretory phase endometrium were approximately one-tenth that in villous trophoblast tissue from human placenta. We did not detect 17fi-HSD type 1 mRNA in endometrial tissue by Northern analysis of total (10 ,.g) RNA. These findings are consistent with the view that the progestinregulated 17(3-HSD of the glandular epithelium of the human endometrium is primarily, if not exclusively, the product of the 17fi-HSD type 2 gene. 17f8-HSD type 2 mRNA Address correspondence to M. Linette Casey, Ph.D., The Cecil H. and Ida Green Center for Reproductive Biology Sciences, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9051. Receivedfor publication 29 April 1994 and in revisedform 28 July 1994. was present in human placenta, liver, and small intestine; much smaller amounts, barely detectable by Northern analysis of poly(A)+ RNA, were present in prostate, kidney, pancreas, and colon, but not in heart, brain, skeletal muscle, spleen, thymus, ovary, or testis. (J. Clin. Invest. 1994. 94:2135-2141.)