Progesterone induction of 17 beta-hydroxysteroid dehydrogenase type 2 during the secretory phase occurs in the endometrium of estrogen-dependent benign diseases but not in normal endometrium

In the human endometrium, inactivation of 17 beta-estradiol to estrone is c atalyzed by 17 beta-hydroxysteroid dehydrogenase type 2 (17 beta HSD2). Pre vious studies have shown that the 17 beta HSD2 activity in the endometrium is elevated during the secretory phase, as compared with the level during t he proliferative phase, and that the elevation is in response to progestero ne 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 (defin ed as "disease free"), but present in the endometrium obtained from patient s with endometriosis, adenomyosis, and/or leiomyomas (defined as "diseased" ). However, the previous 17 beta HSD studies have been performed without di stinguishing between disease-free and diseased endometria. We, therefore, a nalyzed 17 beta HSD2 distinguishing between disease-free and diseased endom etria. During the proliferative phase, the abundance of messenger RNA (mRNA ) and activity of 17 beta HSD2 were comparable in both disease-free and dis eased endometrium. However, during the secretory phase, while the abundance of mRNA and activity of 17 beta HSD2 increased 4- to B-fold in diseased en dometrium, the 17 beta HSD2 remained unchanged in the disease-free endometr ium. Kinetic studies showed that the K-m was identical among the four group s of endometria, suggesting that the elevation of 17 beta HSD2 simply resul ted from increased mRNA transcription. Organ culture of proliferative endom etria in the presence of progestins resulted in the stimulation of 17 beta HSD2 in diseased endometria via the progesterone receptors, whereas disease -free endometrium was not stimulated by progestins. These results suggest t hat the previous paradigm that 17 beta HSD2 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 altere d in the endometria of the patients with estrogen-dependent benign diseases .