CHANGES IN LEVELS OF MESSENGER-RNAS OF TRANSFORMING GROWTH-FACTOR (TGF)-BETA-1, (TGF)-BETA-2, (TGF)-BETA-3, TGF-BETA TYPE-II RECEPTOR AND SULFATED GLYCOPROTEIN-2 DURING APOPTOSIS OF MOUSE UTERINE EPITHELIUM

To examine the roles played by transforming growth factors (TGF)-beta 1, -beta 2, -beta 3, and TGF-beta type II receptors in the induction o f apoptosis in the mouse uterine epithelium after estrogen deprivation , we investigated the expression of their mRNAs and the mRNA of sulfat ed glycoprotein-2 (SGP-2). Pellets containing 100 mu g estradiol-17 be ta (E(2)) were implanted into ovariectomized mice and removed four day s later. Apoptotic indices (percentage of apoptotic cells) of both lum inal and glandular epithelia increased after E(2) pellets were removed , but administration of progesterone (P), 5 alpha-dihydrotestosterone (DHT), or continued implantation of E(2) pellets suppressed this incre ase. Levels of mRNAs of TGF-beta 1, -beta 2, and -beta 3, and SGP-2 di d not increase after estrogen deprivation. However, estrogen deprivati on 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 , E(2), P, and DHT markedly decreased the level of TGF-beta type II re ceptor mRNA. In situ hybridization demonstrated that mRNAs of TGF-beta 1, -beta 2, -beta 3 and TGF-beta type II receptor were localized to t he epithelium. Exogenous administration of TGF-beta 1 into the uterine stroma induced apoptosis in the epithelium, a finding that suggests t hat signals produced by TGF-beta s can induce apoptosis. Therefore, th e present results suggest that increased sensitivity of uterine epithe lial cells to TGF-beta s, as demonstrated by an increase in TGF-beta t ype II receptor mRNA, is involved in the induction of apoptosis after estrogen deprivation, although signals produced by TGF-beta s do not a ppear sufficient to induce apoptosis. Copyright (C) 1996 Elsevier Scie nce Ltd.