Undernutrition, Puberty and the Development of Estrogen Positive Feedback in the Female Rat1

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Abstract
The development of the positive feedback of estrogen in normally fed animals and its possible alterations in animals subjected to restricted food intake was studied. Different doses of estradiol benzoate (EB), administered s.c. as a single injection to normal prepubertal rats of different ages, resulted in an increase in uterine weight which became more prominent as the animals approached puberty. Significant gonadotropin release was induced by EB only from Day 26 on. The LH response to EB measured in the afternoon (1600 h) of the second day following the injection increased with age; the older rats showing an elevation in LH levels after the administration of doses of EB which were ineffective in younger rats. In rats injected with the highest dose of EB (5 µg/100 g bw), gonadotropin release occurred 1 day earlier. Modification of the growth rate of rats by varying the milk supply during the nursing period, followed by normal postweaning feeding, revealed that attainment of a critical body weight is not essential for puberty to occur since animals reached puberty at the same age, but at different body weights. Other animals maintained after weaning under restricted diet did not reach puberty for as long as their access to food was restricted (Day 57). When food was made available ad libitum, vaginal opening and ovulation occurred within a week. At 42 days of age, the underfed rats had small uteri and restoration of food produced a dramatic increase in uterine weight and gonadotropin levels. At this age, the underfed rats responded to EB injection with a remarkable increase in gonadotropins which was even greater than that induced by a similar dose of EB in younger normally fed rats of similar body weight. Restoration of food followed by ES injection resulted in ovulation within 3 days. The results indicate that 1) the gonadotropin response to estrogen positive feedback develops gradually and quantitatively as the animal matures and 2) undernutrition-induced delayed puberty is not caused by inability of the hypothalamic-pituitary unit to respond to positive estrogen feedback, but rather to ovarian failure to release estrogen in amounts sufficient to trigger a gonadotropin surge. However, the fact that in underfed rats, basal gonadotropin levels were not elevated indicates that the steroid negative feedback was operative in these animals.