title: Changes in levels of mRNAs of transforming growth factor (TGF)-beta1, -beta2, -beta3, TGF-beta type II receptor and sulfated glycoprotein-2 during apoptosis of mouse uterine epithelium.
abstract: To examine the roles played by transforming growth factors (TGF)-beta1, -beta2, -beta3, and TGF-beta type II receptors in the induction of apoptosis in the mouse uterine epithelium after estrogen deprivation, we investigated the expression of their mRNAs and the mRNA of sulfated glycoprotein-2 (SGP-2). Pellets containing 100 microg estradiol-17beta (E2) were implanted into ovariectomized mice and removed four days later. Apoptotic indices (percentage of apoptotic cells) of both luminal and glandular epithelia increased after E2 pellets were removed, but administration of progesterone (P), 5alpha-dihydrotestosterone (DHT), or continued implantation of E2 pellets suppressed this increase. Levels of mRNAs of TGF-beta1, -beta2, and -beta3, and SGP-2 did not increase after estrogen deprivation. However, estrogen deprivation caused a gradual increase in the level of TGF-beta type II receptor mRNA, and its level increased about six-fold six days later. Moreover, E2, P, and DHT markedly decreased the level of TGF-beta type II receptor mRNA. In situ hybridization demonstrated that mRNAs of TGF-beta1, -beta2, -beta3 and TGF-beta type II receptor were localized to the epithelium. Exogenous administration of TGF-beta1 into the uterine stroma induced apoptosis in the epithelium, a finding that suggests that signals produced by TGF-betas can induce apoptosis. Therefore, the present results suggest that increased sensitivity of uterine epithelial cells to TGF-betas, as demonstrated by an increase in TGF-beta type II receptor mRNA, is involved in the induction of apoptosis after estrogen deprivation, although signals produced by TGF-betas do not appear sufficient to induce apoptosis.
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University Medical School, Suita, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Wada
authors.forename: S
authors.initials: S
authors.lastname: Nomura
authors.forename: E
authors.initials: E
authors.lastname: Morii
authors.forename: Y
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Y
authors.initials: Y
authors.lastname: Nishizawa
authors.forename: A
authors.initials: A
authors.lastname: Miyake
authors.forename: N
authors.initials: N
authors.lastname: Terada
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015152:Blotting, Northern; D051152:Clusterin; D003907:Dexamethasone / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D004967:Estrogens / Q000172:deficiency / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D017403:In Situ Hybridization; D051379:Mice; D008807:Mice, Inbred BALB C; D018832:Molecular Chaperones; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000096:biosynthesis; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D014599:Uterus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: C495243:Clu protein, mouse; D051152:Clusterin; D004967:Estrogens; D006023:Glycoproteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D013196:Dihydrotestosterone; D011374:Progesterone; D004958:Estradiol; D003907:Dexamethasone; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II