ANALOGOUS TAMOXIFEN AND ESTROGEN EFFECTS ON TRANSFORMING GROWTH-FACTOR-BETA-1 AND GROWTH-FACTOR-BETA-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 bre ast cancer trials have established that tamoxifen also increases uteri ne cancer risk. In this report, uteri of oophorectomized rats were exa mined to ascertain the effects of estrogen and tamoxifen on the uterin e induction of two isoforms of transforming growth factor-beta (TGF-be ta). In contrast to studies of cells derived from breast epithelium, o ur studies reveal that both estrogen and tamoxifen increase immunoreac tive TGF-beta. These changes were particularly pronounced in the endom etrial stroma. Effects of progesterone also were examined and found to be distinct and relatively restricted to the glandular epithelium. Th ese studies indicate that, in the uteri of oophorectomized rats, tamox ifen exerts estrogen-like effects on a peptide previously implicated i n the control of cellular growth and differentiation. We hypothesize t hat induction of TGF-beta isoforms may be an important mediatior of bo th estrogen- and tamoxifen-induced proliferative disorders in the uter us.