Long-term effects of postnatal exposure to diethylstilbestrol on uterine estrogen receptor and growth.
Diethylstilbestrol (DES) treatment of female rats on postnatal days (PND) 1-5 reduces uterine growth, estrogen receptor (ER) level and gland number by PND 25, while daily DES treatment on PND 1-25 increases uterine growth 4-fold, further reduces ER level and completely suppresses gland formation. We now report the persistence of these effects in adults. By PND 60, uterine weight was 70% of controls in rats injected with DES on PND 1-5 but only 10% of controls in rats injected PND 1-10 or longer. In fact, uterine weights were the same on PND 10 and 60. Uterine gland numbers were reduced to 30% of controls in all DES-treated rats regardless of exposure length; however, luminal and glandular epithelial cell heights were reduced to less than 50 and 70%, respectively, of controls when DES was given on PND 1-25 but not when given on PND 1-5. Ovariectomy 7 days prior to sacrifice on PND 60 reduced uterine weight in controls by 67% and in rats injected with DES on PND 1-5 by 53%, but had no effect in rats injected with DES on PND 1-10. DES exposure at either PND 1-5 or 1-10 lowered ER levels by 35-50% at both 60 and 90 days. Treatment with a high dose of estradiol (E2) 1 week before sacrifice significantly down-regulated ER to the same concentration in all treatment groups at PND 60 and 90. Following E2 treatment, all groups also showed increased uterine weight at PND 60 and 90. These data show there is a short period of development (PND 5-10) in which further DES exposure indirectly inhibits uterine growth.
Medlock
K L
KL
Department of Health and Human Services, Food and Drug Administration, National Center for Toxicological Research, Division of Reproductive and Development Toxicology, Jefferson, AR 72079-9502.
Branham
W S
WS
Sheehan
D M
DM
D000375:Aging; D000818:Animals; D004054:Diethylstilbestrol / Q000008:administration & dosage / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000378:metabolism*; D014599:Uterus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism
D011960:Receptors, Estrogen; D004054:Diethylstilbestrol