Etiology of DES-induced uterine tumors in the Syrian hamster.
This paper describes a new experimental model system for the induction of endometrial adenocarcinoma in hamster uterus following diethylstilbestrol (DES) treatment of the newborn female. We propose that DES acts as an initiator during early development and that other estrogens act as promoters to stimulate tumor development in the adult uterus. DES directly affects the uterus as was shown by the failure of neonatal ovariectomy to prevent early DES-induced uterine growth. Subsequently, ovarian estrogen secretion from anovulatory, polyfollicular ovaries modifies the DES-altered uterus starting between 20 and 30 days of age and continuing into adult life. Early DES effects on the uterus include stimulation of endometrial cellular differentiation and progesterone receptor production. Permanent changes in uterine collagen, DNA and progesterone receptor content were noted, but the responsiveness of the DES-altered uterus to estrogen and progestin action was not impaired. Morphogenetic changes included an increase in extracellular connective tissue elements and striking alterations in endometrial cell composition such as hyperplasia of luminal and glandular epithelia and a massive inflammatory response in the stroma. Endometrial adenocarcinomas occurred in DES-treated animals in association with exposure to either endogenous estrogen from anovulatory ovaries or exogenous estrogen treatment of the ovariectomized animal. Endometrial tumors had relatively high concentrations of estrogen and progesterone receptors, suggesting a sensitivity to hormone action. Thus, these studies (a) demonstrate the utility of this animal model for the preparation of experimental endometrial tumors, and (b) suggest that DES acts as an initiator to transform uterine cells during early development, and estrogen exposure later in life acts as a promotor to stimulate growth and proliferation of DES-transformed cells.
D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D006224:Cricetinae; D004054:Diethylstilbestrol / Q000633:toxicity*; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D008647:Mesocricetus; D009374:Neoplasms, Experimental / Q000139:chemically induced; D011372:Progestins / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D014594:Uterine Neoplasms / Q000032:analysis / Q000139:chemically induced*; D014599:Uterus / Q000473:pathology
D004967:Estrogens; D011372:Progestins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D004958:Estradiol; D004054:Diethylstilbestrol