Sexual differentiation of the luteinizing hormone response of neonatal rats to the narcotic antagonist naloxone: critical role of estrogen receptors.
Administration of the narcotic antagonist naloxone results in an elevation of serum luteinizing hormone (LH) levels in 10-day-old female, but not male, rats. Previous studies from this laboratory indicated a role for neonatal gonadal steroids in the development of this sex-specific response. In this study, the estrogen receptor antagonist OH-Tamoxifen or the androgen-receptor antagonist flutamide were injected on Days 1 or 9 of life, and the LH responses of male and female pups to naloxone were assessed on Day 10. Flutamide did not produce a response different from that seen in vehicle-treated pups, discounting a role for androgen receptors. OH-Tamoxifen on Day 9 caused an increase in basal levels of LH; neither sex showed a response to naloxone. However, OH-Tamoxifen treatment of 1-day-old males resulted in an enhanced release of LH upon challenge with naloxone on Day 10 of life; similar treatment of 1-day-old females resulted in a normal female-type response to the opioid antagonist. These results show that blockade of estrogen receptors in males during the "critical period" of sexual differentiation results in a female phenotypic response to naloxone. Therefore, estrogen receptors play a critical role in the sexual differentiation of the LH response to naloxone in neonatal male rats.
Almeida
O F
OF
Department of Neuropharmacology, Max-Planck-Institut für Psychiatrie, Planegg-Martinsried, F.R.G.
Schulz
R
R
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood*; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000187:drug effects*; D012727:Sex Characteristics; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology
D011960:Receptors, Estrogen; D013629:Tamoxifen; C016601:afimoxifene; D009270:Naloxone; D005485:Flutamide; D007986:Luteinizing Hormone