SEXUAL PRECOCITY AFTER EXPOSURE OF INFANT FEMALE RATS

25 An increase in frequency of pulsatile GnRH secretion in vitro and a reduction in LH 26 response to GnRH in vivo characterize hypothalamic-pituitary maturation before puberty in the 27 female rat. In girls migrating for international adoption, sexual precocity is frequent and could 28 implicate former exposure to the insecticide DDT since a long lasting DDT derivative has been 29 detected in the serum of such children. We aimed at studying the effects of early transient 30 exposure to E2 or DDT in vitro and in vivo in the infantile female rat. Using a static incubation 31 system of hypothalamic explants from 15-day-old female rats, a concentrationand time32 dependent reduction in GnRH interpulse interval (IPI) was seen during incubation with E2 and 33 DDT isomers. These effects were prevented by antagonists of AMPA/kainate receptors and ER. 34 Also, o,p’-DDT effects were prevented by an antagonist of the AHR. After s.c. injections of E2 35 or o,p’-DDT between PND 6 and 10, a decreased GnRH IPI was observed on PND 15 as an ex 36 vivo effect. After DDT administration, serum LH levels in response to GnRH were not different 37 from controls on PND 15 while they tended to be lower on PND 22. Subsequently, early VO and 38 first estrus were observed together with a premature age-related decrease in LH response to 39 GnRH. After prolonged exposure to E2 between PND 6 and 40, VO occurred at an earlier age but 40 first estrus was delayed. We conclude that a transient exposure to E2 or o,p’-DDT in early 41 postnatal life is followed by early maturation of pulsatile GnRH secretion and, subsequently, 42 early developmental reduction of LH response to GnRH that are possible mechanisms of the 43 subsequent sexual precocity. The early maturation of pulsatile GnRH secretion could involve 44 effects mediated through ER and/or AHR as well as AMPA/kainate subtype of glutamate 45 receptors. 46