EFFECTS OF CHANGES IN NUTRITIONAL CONDITIONS ON TIMING OF PUBERTY - CLINICAL-EVIDENCE FROM ADOPTED-CHILDREN AND EXPERIMENTAL STUDIES IN THE MALE-RAT

Among 32 patients with idiopathic central precocious puberty seen during a 3-year period, 1/4 were adopted children from developing countries who showed early sexual maturation during the catch-up process following their arrival in Belgium. To study the possible mechanism accounting for such clinical observations, we used the male rat as a model, and evaluated the effect of variations in early nutritional conditions, by manipulating litter size, on hypothalamic and testicular maturation. We had shown previously that, in the male rat, onset of puberty was preceded, between 15 and 25 days of age, by a transiently increased activation of N-methyl-D-aspartate receptors involved in a facilitatory control of pulsatile secretion of gonadotropin-releasing hormone. We also showed that the proportion of elongated spermatids in testicular cell homogenates increased between 25 and 45 days of age. When compared to pups of a small litter (6/dam), those of a large litter (14/dam) showed a reduced growth rate (1.9 vs. 3.5 g/day) before weaning (21 days), whereas they grew at a similar rate (5.6 vs. 4.7 g/day) after weaning. At 35 days of age, the animals raised in the large litter showed evidence of delayed hypothalamic and testicular maturation when compared to animals from the small litter. Reduction of litter size at 17 days allowed food-restricted pups of a large litter to resume a normal growth rate before weaning. Then, the level of hypothalamic and testicular maturation studied at 20 and 35 days was similar to that of rats raised in a small litter, although these well-fed animals were significantly bigger than those from the large litter refed at 17 days. Serum concentrations of insulin-like growth factor I were lower in food-restricted animals refed after weaning than in rats well-fed or refed before weaning. When food-restricted pups were allowed to resume a normal growth rate at 12 days, they showed, at 15 days, evidence of earlier hypothalamic maturation than well-fed rats, despite being significantly smaller. In summary, the increase in growth rate resulting from unrestricted feeding after nutritional deprivation was associated with accelerated hypothalamic and testicular maturation which were advanced for body size. However, such an effect was only observed when refeeding occurred before weaning, indicating that hypothalamic maturation was sensitive to changes in nutritional conditions and growth rate during a critical period preceding the onset of puberty.