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We tested the hypothesis that neonatal treatment of rats with testosterone propionate (TP) or estradiol benzoate (EB) reduces the uterine responsiveness to estradiol and reduces the concentration of estrogen "receptor" before puberty, and that both of these events precede the onset of the persistent estrus syndrome. Thre-day-old female rats were injected with 100 mug 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 mug/kg body weight estradiol-17beta was injected at 22 and 30 days of age and uterine wiights 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 futher experiment in rats ovariectomized at 9 days of age, those treated neonatally with EB had significantly smaller uteri than their untreated ovariectomized controls, thus providing indirect evidence for an extravarian 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.

The sex steroid-binding protein (rSBP) of immature rabbit serum was purified to homogeneity by the sequential use of DEAE-cellulose chromatography, affinity chromatography on 5alpha-dihydrotestosterone-17 beta-succinyl-diaminoethyl-(1,4-butanediol diglycidyl ether)-agarose, agarose (Bio-Gel-A-0.5m) gel filtration, and preparative polyacrylamide gel electrophoresis. The cumulative yield is 13%. Homogeneity of rSBP was shown by the equilibrium sedimentation ultracentrifugation in 6 M guanidine HCl containing 0.1 M mercaptoethanol which yields an average molecular weight of 36,475 +/- 865. Analytical gel electrophoresis in the presence of sodium dodecyl sulfate and gel filtration on agarose yield a molecular weight of 57,000 and 120,000, respectively. The variation is due to a 30% carbohydrate content. The amino acid composition is reported. Comparison of the rabbit and human SBP indicate that they are different in both their molecular and functional properties.