Neonatal Treatment with Sex Steroids: Relationship Between the UterotropicResponse and the Estrogen “Receptor” in Prepubertal Rats1

Abstract

Neonatal treatment of rats with testosterone propionate (TP) or estradiol benzoate (EB) night reduce the uterine responsiveness to estradiol and reduce the concentration of estrogen receptor before puberty, and both of these events might precede the onset of the persistent estrus syndrome. Three-day-old female rats were injected with 100 .mu.g EB, TP or sesame oil (controls) and at 23 and 31 days of age (before the onset of puberty) the uterine cytoplasmic content of specific 8S estradiol-binding protein was measured by sucrose density gradients. Binding by the nuclear fraction was also measured utilizing an exchange assay. In a subgroup of rats also treated neonatally, 2 .mu.g/kg body weight estradiol-17.beta. was injected at 22 and 30 days of age and uterine weights were measured as a test for uterine responsiveness. At 23 and 31 days of age the uterine cytoplasmic 8S estrogen receptor was significantly reduced in the EB-treated rats, but the uterotropic response to estradiol was blocked only in the 23 day old rats; the uterine response at 31 days was slightly, but not significantly, reduced. In contrast, neonatally administered TP had no effect on either the concentration of cytoplasmic estradiol-binding sites or uterine responsiveness. Nuclear binding of estradiol was unaffected by either TP or EB treatment in both age groups. In a further experiment in rats ovariectomized at 9 days of age, those treated neonatally with EB had significantly smaller uteri than their untreated ovariectomized controls, providing indirect evidence for an extraovarian factor affected by neonatal treatment. These data support the hypothesis that neonatal EB treatment may directly inhibit the synthesis or replenishment of the 8S estradiol receptor prior to the development of the persistent estrus syndrome (persistent vaginal estrus, anovulation and polycystic ovaries). A neonatally-induced neuroendocrine disorder affecting steroid secretion by the ovary or adrenal may also exist prepubertally to account for the uterine defects.