Defective estrogen receptor in uteri of rats treated neonatally with a high dose of estrogen.

The female Sprague-Dawley rats were daily injected with 100 micrograms of estradiol-17beta from the day of birth to 10 days of age. All these neonatally estrogenized rats exhibited a state of persistent vaginal diestrus after attainment of puberty. When 3H-estradiol-17beta was administered, the radioactivity in the uteri of the estrogenized postpubertal rats was significantly reduced, compared to that in the untreated rats. Otherwise, there was no significant difference of the radioactivity in the liver, diaphragm, and serum between the estrogenized and untreated groups. Uterine estrogen receptor having a sedimentation constant of 8S was demonstrated in the untreated immature and mature rats by sucrose density gradient centrifugation, whereas there was no detectable estrogen binding components in the uterine cytosol from the estrogenized postpubertal rats, irrespective of the date of autopsy. No discernible changes in the sedimentation profiles could be observed in the estrogenized postpubertal rats after oophorectomy. The results suggest that high doses of estrogen administered in the estrogen administered neonatally to female rats may couse permanent deficiency of uterine estrogen receptor and result in uterine insensitiveness to estrogen in their later lives.