Impaired prepubertal uterine responsivity after neonatal exposure to steroid hormone esters

Abstract

Injection of neonatal rats on day 3 after birth with a single dose of 5 microgram or 100 microgram estradiol benzoate (EB) or 30 microgram or 1,250 microgram testosterone propionate (TP) drastically impairs the development of uterine growth response to exogenous estradiol on day 21 of life. Reduction of uterine responsivity was augmented by EB treatment compared to TP treatment. This may be explained by an apparent reduction in available cytoplasmic estrogen binding sites in the uterus with a concomitant decrease in nuclear retention of the receptor-estrogen complex which was in addition to the effect upon estrogen-stimulated metabolic activity (glucose oxidation) resultant from either TP or EB exposure. The degree of reduced uterine responsivity at 21 days of age directly corresponds to the degree of reduction in the ovarian weights observed in the neonatally treated rats. Neonatal ovariectomy on day 3 of life also produced a uterine response syndrome characteristic of neonatal estrogenization. Thus, it is suggested that endogenous estrogen secretion during infancy may be important in end organ conditioning in the development of a functionally competent uterus.

Effect of neonatal exposure to the antioestrogens nafoxidine and CI-628 upon the development of the uterus in the prepubertal rat

“…The ovarian weight reduction observed in the prepubertal rat treated neonatally with steroid ester or antioestrogen probably represents feedback suppression of gonadotrophin secretion due to the introduction of exogenous agonist (Clark et al, 1973;Geliert et al, 1977;Campbell, 1980). Additionally, previous reports have demonstrated a causal relationship between prepubertal ovarian weights and uterine sensitivity to oestrogen-stimulated growth or glucose oxidation (Campbell, 1980;Campbell & Modlin, 1987). In this regard, neonatal treatment with CI-628, unlike nafoxidine, is without effect upon development of the uterine phosphogluconate oxidative pathway, and CI-628 treatment does not result in the reduction of prepubertal ovarian weights to the same extent as do other treatments.…”

“…It has been previously demonstrated (Geliert et al, 1977; Campbell, 1980) that neonatal adminis¬ tration of oestradiol benzoate results in impaired uterine growth responses to exogenous oestradiol in the prepubertal rat. This reduction in uterine responsivity is the result of a decrease in available cytoplasmic oestrogen binding sites in the uterus with a concomitant decrease in the nuclear reten¬ tion of the receptor-oestrogen complex by uterine nuclei (Geliert et al, 1977;Campbell, 1980). Additionally, neonatal exposure to oestradiol benzoate impairs the capacity of the uterus to metabolize glucose under oestrogen stimulation (Campbell, 1980).…”

“…This reduction in uterine responsivity is the result of a decrease in available cytoplasmic oestrogen binding sites in the uterus with a concomitant decrease in the nuclear reten¬ tion of the receptor-oestrogen complex by uterine nuclei (Geliert et al, 1977;Campbell, 1980). Additionally, neonatal exposure to oestradiol benzoate impairs the capacity of the uterus to metabolize glucose under oestrogen stimulation (Campbell, 1980). The latter effect augments the severity of disturbance of uterine function by neonatal oestrogenization in contrast to that produced by neonatal androgenization.…”

Perinatal exposure to androgen excess and the effects on the rat uterine estradiol responsiveness

“…Although Gellert et al () did not find any significant effect on uterine response to estrogen after neonatal androgen exposure in prepubertal rats, others have reported a decrease in this responsiveness (Lobl, ; Lobl and Maenza, ; Campbell, ; Schwartz et al, ; Campbell and Modlin, ). Such discording results may be because androgenization exerts different effects according to the stage of development in which fetuses or neonatal animals are exposed (Lobl and Gorski, ; MacLusky and Naftolin, ; Arriaza et al, ).…”

Uterine glucose metabolism in the prepubertal rat treated neonatally with androgen, estrogen, and antihormones

“…The reproductive impairment in the adult is preceded by altered reproductive tissue function in the immature rat s, 6. One aspect, impaired uterine growth responsivity evident in the androgenized or estrogenized prepubertal rat, is the consequence of decreased function of the hypothalamic-pituitary-ovarian axis 6.…”