Retinoic acid inhibits estrogen-induced uterine stromal and myometrial cell proliferation.
Retinoic acid, a potent natural derivative of vitamin A, influences proliferation in many cell types. However, little is known about the role of retinoic acid in estrogen-induced proliferation in normal physiological systems. In this study we sought to determine if in vivo administration of retinoic acid influences the proliferation of a normal estrogen target tissue, the immature rat uterus. The results indicate that treatment of animals with 30 mg/kg all-trans-retinoic acid for 3 days before 17 beta-estradiol (E2) administration diminishes DNA synthesis and cell division by approximately 50% in uterine stromal and myometrial cells. Luminal epithelial cell proliferation is not inhibited, indicating that the antiproliferative effects of all-trans-retinoic acid treatment are cell type-specific. The inhibition is retinoid-specific and fully reversible 1 week after discontinuing all-trans-retinoic acid treatment. The inhibitory effect of all-trans-retinoic acid is not due to a change in E2 receptor levels assessed by ligand binding. E2 induction of c-jun, a gene expressed primarily in myometrial cells, is unaffected in retinoid-treated animals. This is the first demonstration that retinoic acid inhibits estrogen-induced proliferation of uterine stromal and myometrial cells in a physiological setting.
Boettger-Tong
H L
HL
Department of Pharmacology, University of Texas Medical School at Houston 77225, USA.
Stancel
G M
GM
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D004247:DNA / Q000096:biosynthesis; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects; D007700:Kinetics; D009215:Myometrium / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017154:Stromal Cells / Q000166:cytology; D014212:Tretinoin / Q000494:pharmacology*; D014599:Uterus / Q000166:cytology*
D004958:Estradiol; D014212:Tretinoin; D004247:DNA