Environment

Early Maturation of Gonadotropin-Releasing Hormone Secretion and Sexual Precocity after Exposure of Infant Female Rats to Estradiol or Dichlorodiphenyltrichloroethane

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

Key words: Environment • Estradiol • Gonadotropin-releasing hormone • Hypothalamus • Puberty

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