Variations in pituitary-gonadal suppression during intranasal buserelin and intramuscular depot-triptorelin therapy for central precocious puberty. Belgian Study Group for Pediatric Endocrinology.

This study evaluated pubertal development, growth and pituitary-gonadal suppression in 21 patients with central precocious puberty treated with buserelin intranasally and switched after a mean of 2.1 yr to depot-triptorelin given im for 1 year. Arrest or regression of puberty was observed in 12 patients while progression of puberty during therapy was seen in 9 patients (6 on buserelin, 2 on triptorelin and 1 on both therapies). The increment in serum LH and FSH concentrations after sc injection of short-acting triptorelin was greater on buserelin than on triptorelin therapy, particularly in patients with evidence of progression of puberty. Height velocity during therapy showed a reduction which paralleled the decelerating phase of the normal pubertal growth spurt. The rate of bone maturation during therapy was inversely related to pretreatment bone age. Predicted final height showed marked individual variations which were inversely related to predicted adult height before therapy. These data indicate that differences in the nature and route of administration of Gn-RH agonist therapy for central precocious puberty can be of importance for inhibition of pituitary gonadotropin secretion and development of secondary sex characteristics. Height velocity and bone maturation are age-related and the change in predicted adult height depends on pretreatment level.

Gonadal-independent developmental changes in activation of N-methyl-D-aspartate receptors involved in gonadotropin-releasing hormone secretion.

Using hypothalamic explants of male rats, we have shown that the N-methyl-D-aspartate (NMDA) receptors involved in a stimulatory control of gonadotropin-releasing hormone (GnRH) secretion were transiently activated at 25 days around the time of onset of puberty. This was evidenced by studying the dose-related inhibition of veratridine-induced GnRH secretion by MK-801, a use dependent antagonist of NMDA receptors. An increase in sensitivity of GnRH secretion to the inhibitory effect of MK-801 was used as a marker of increased activation of NMDA receptors involved in stimulation of GnRH secretion. Here, we report on data obtained in intact and castrated rats at different ages. The aim was to determine whether the absence of gonads would affect the developmental changes in activation of NMDA receptors that we described recently. In pubertal (50-day-old) rats, orchidectomy resulted in an activation of NMDA receptors which was nonsignificant after 4 days but significant after 13 days. In prepubertal rats orchidectomized at 5 or 10 days and studied 10 days later, the NMDA receptors involved in GnRH secretion were also more activated than in intact animals. Using explants of intact and castrated animals, a similar increase in activation of NMDA receptors was observed between 15 and 25 days of age, a period preceding onset of puberty. Subsequently, between 25 and 50 days, a reduction in NMDA receptor activation was seen. This decrease was observed in intact rats showing normal sexual development and in castrated rats as well.(ABSTRACT TRUNCATED AT 250 WORDS)

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.(ABSTRACT TRUNCATED AT 250 WORDS)