Expression analysis of the genes involved in estradiol and progesterone action in human ovarian endometriosis.
Endometriosis is defined as the presence of endometrial glands and stroma within extrauterine sites, and it is well known that endometriosis is an estrogen-dependent disease. The defective formation and metabolism of steroid hormones is responsible for the promotion and development of endometriosis. In the present study we examined the mRNA levels of six enzymes that are involved in the metabolism of estrogen and progesterone--aromatase, 17beta-hydroxysteroid dehydrogenase (17beta-HSD) types 1, 2 and 7, sulfatase and sulfotransferase--and of the steroid receptors--estrogen receptors alpha and beta (ERalpha, ERbeta) and progesterone receptors A and B (PRAB)--implicated in human ovarian endometriosis. We analyzed 16 samples of ovarian endometriosis and 9 of normal endometrium. The real-time polymerase chain reaction analyses revealed that six of the nine genes investigated are differentially regulated. Aromatase, 17beta-HSD types 1 and 7, sulfatase and ERbeta were statistically significantly upregulated, while ERalpha was significantly downregulated, in the endometriosis group compared with the control group. There were no significant differences in 17beta-HSD type 2, sulfotransferase and PRAB gene expression. Our results indicate that, in addition to the previously reported upregulation of aromatase, upregulation of 17beta-HSD types 1 and 7 and sulfatase can also increase the local estradiol concentration. This could thus be responsible for the estrogen-dependent growth of endometriotic tissue. Surprisingly ERalpha was downregulated.
Smuc
Tina
T
Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrasov trg. 2, 1000 Ljubljana, Slovenia.
Pucelj
Martina Ribic
MR
Sinkovec
Jasna
J
Husen
Bettina
B
Thole
Hubert
H
Lanisnik Rizner
Tea
T
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D004715:Endometriosis / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D010049:Ovarian Diseases / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D043266:Steryl-Sulfatase / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
D047628:Estrogen Receptor alpha; D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases; D001141:Aromatase; D043266:Steryl-Sulfatase