Early postnatal androgenization imprints selective changes in the action of estrogens in the rat uterus

Abstract

Exposure of animals perinatally to some hormonally active agents may imprint permanent changes on the action of related hormones. The present study investigated the effects of early postnatal androgenization on various genomic responses to estrogen in the uterus of prepubertal rats. Female rats were androgenized at postnatal ages of 1, 5, or 13 days with a single s.c. injection of testosterone propionate. At the age of 21 days, the animals were stimulated with estrogens. The uteri of androgenized and control rats were analyzed morphometrically to measure genomic parameters of estrogen stimulation in the uterus. The results demonstrate that early postnatal androgenization does not equally affect all uterine cell types and that the effects of androgenization change according to the age at androgenization. The dissociation between the various responses according to the time of androgenization suggests that there are critical ages at which the uterine cell types that respond to estrogens can be altered permanently by imprinting. The finding of changes in the action of estrogen induced by androgenization at older than neonatal ages in the rat suggests that similar changes may occur in humans exposed to androgens during their extrauterine life. This result also points to the need for further studies using the rhesus monkey because of its close resemblance to the human with respect to female reproductive physiology.