Analogous tamoxifen and estrogen effects on transforming growth factor-betas 1 and 2 in the rat uterus.
Estrogenic stimulation is a potent risk factor for the development of uterine cancer. More recently, analysis of patients in prospective breast cancer trials have established that tamoxifen also increases uterine cancer risk. In this report, uteri of oophorectomized rats were examined to ascertain the effects of estrogen and tamoxifen on the uterine induction of two isoforms of transforming growth factor-beta (TGF-beta). In contrast to studies of cells derived from breast epithelium, our studies reveal that both estrogen and tamoxifen increase immunoreactive TGF-beta. These changes were particularly pronounced in the endometrial stroma. Effects of progesterone also were examined and found to be distinct and relatively restricted to the glandular epithelium. These studies indicate that, in the uteri of oophorectomized rats, tamoxifen exerts estrogen-like effects on a peptide previously implicated in the control of cellular growth and differentiation. We hypothesize that induction of TGF-beta isoforms may be an important mediator of both estrogen- and tamoxifen-induced proliferative disorders in the uterus.
Sartor
B M
BM
Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland, USA.
Sartor
O
O
Flanders
K C
KC
D000818:Animals; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000187:drug effects*; D014599:Uterus / Q000737:chemistry / Q000187:drug effects*
D004967:Estrogens; D016212:Transforming Growth Factor beta; D013629:Tamoxifen; D011374:Progesterone