title: Progesterone induction of 17beta-hydroxysteroid dehydrogenase type 2 during the secretory phase occurs in the endometrium of estrogen-dependent benign diseases but not in normal endometrium.
abstract: In the human endometrium, inactivation of 17beta-estradiol to estrone is catalyzed by 17beta-hydroxysteroid dehydrogenase type 2 (17betaHSD2). Previous studies have shown that the 17betaHSD2 activity in the endometrium is elevated during the secretory phase, as compared with the level during the proliferative phase, and that the elevation is in response to progesterone via the progesterone receptors. Recently, it has been demonstrated that aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis, is not present in the endometrium obtained from normal menstruating women with cervical cancer in situ showing no other gynecological disease (defined as "disease free"), but present in the endometrium obtained from patients with endometriosis, adenomyosis, and/or leiomyomas (defined as "diseased"). However, the previous 17betaHSD studies have been performed without distinguishing between disease-free and diseased endometria. We, therefore, analyzed 17betaHSD2 distinguishing between disease-free and diseased endometria. During the proliferative phase, the abundance of messenger RNA (mRNA) and activity of 17betaHSD2 were comparable in both disease-free and diseased endometrium. However, during the secretory phase, while the abundance of mRNA and activity of 17betaHSD2 increased 4- to 6-fold in diseased endometrium, the 17betaHSD2 remained unchanged in the disease-free endometrium. Kinetic studies showed that the Km was identical among the four groups of endometria, suggesting that the elevation of 17betaHSD2 simply resulted from increased mRNA transcription. Organ culture of proliferative endometria in the presence of progestins resulted in the stimulation of 17betaHSD2 in diseased endometria via the progesterone receptors, whereas disease-free endometrium was not stimulated by progestins. These results suggest that the previous paradigm that 17betaHSD2 activity in the endometrium is elevated during the secretory phase is confined to diseased endometrium but not to disease-free endometrium and that the estrogen metabolism is altered in the endometria of the patients with estrogen-dependent benign diseases.
authors.affiliation: Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Japan. kitawaki@koto.kpu-m.ac.jp
authors.forename: J
authors.initials: J
authors.lastname: Kitawaki
authors.forename: H
authors.initials: H
authors.lastname: Koshiba
authors.forename: H
authors.initials: H
authors.lastname: Ishihara
authors.forename: I
authors.initials: I
authors.lastname: Kusuki
authors.forename: K
authors.initials: K
authors.lastname: Tsukamoto
authors.forename: H
authors.initials: H
authors.lastname: Honjo
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis*; D000293:Adolescent; D000328:Adult; D015152:Blotting, Northern; D016889:Endometrial Neoplasms / Q000201:enzymology; D004715:Endometriosis / Q000201:enzymology*; D004717:Endometrium / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D004967:Estrogens / Q000502:physiology*; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000201:enzymology; D008597:Menstrual Cycle / Q000378:metabolism*; D008875:Middle Aged; D009924:Organ Culture Techniques; D011374:Progesterone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004967:Estrogens; D012333:RNA, Messenger; D011374:Progesterone; D015067:17-Hydroxysteroid Dehydrogenases