Genetic variation in physiological sensitivity to estrogen in mice.
Genetic variation in susceptibility to endocrine disruption by estrogenic agents was examined in juvenile male mice. Mice were implanted with increasing doses of estradiol (E2) at 3 weeks of age and reproductive responses were determined 3 weeks later. Greater than 16-fold differences in susceptibility to the disruption of reproductive development by E2 were detected between strains of mice. CD-1 was much more resistant to the inhibition of testes weight, vesicular gland weight and spermatogenesis by increasing doses of E2. Spermatid maturation was eliminated by low doses of E2 in unselected strains such as C17/Jls and C57BL/6J. In contrast, widely used, large litter size selected CD-1 mice showed little or no inhibition in spermatogenesis even in response to 16-fold higher doses of E2. Testicular sulfotransferase activity (EST) per gram body weight was 3.5-fold higher in untreated CD-1 than in B6 strain males. This suggests that genetic differences in testicular EST activity may play a critical role in the detoxification of estrogens. These and other findings emphasize the need to identify and study genetic variation in sensitivity to estrogen in laboratory animal models used to assess the risk of xenobiotic estrogen exposure.
Spearow
J L
JL
Section of Neurobiology, Physiology and Behavior, University of California at Davis, 95616, USA. jlspearow@ucdavis.edu
O'Henley
P
P
Doemeny
P
P
Sera
R
R
Leffler
R
R
Sofos
T
T
Barkley
M
M
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004343:Drug Implants; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D014644:Genetic Variation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics*; D008815:Mice, Inbred Strains / Q000235:genetics*; D009929:Organ Size / Q000187:drug effects; D012016:Reference Values; D012098:Reproduction / Q000187:drug effects / Q000502:physiology*; D012669:Seminal Vesicles / Q000033:anatomy & histology / Q000187:drug effects* / Q000254:growth & development; D013045:Species Specificity; D013091:Spermatogenesis / Q000187:drug effects*; D015238:Sulfotransferases / Q000378:metabolism; D013737:Testis / Q000033:anatomy & histology / Q000187:drug effects* / Q000254:growth & development
D004343:Drug Implants; D004958:Estradiol; D015238:Sulfotransferases