Alterations in opioid parameters in the hypothalamus of rats with estradiol-induced polycystic ovarian disease.
The distribution and density of selectively labeled mu-, delta-, and kappa-opioid binding sites were examined by in vitro radioautography in the hypothalamus of normal, estradiol valerate (EV)-injected, and estradiol (E2)-implanted female rats. Hypothalamic beta-endorphin concentration was also examined by RIA in these three groups of animals. Quantitative analysis of film radioautographs demonstrated a selective increase in mu-opioid binding in the medial preoptic area of EV-treated, but not of E2-implanted rats. However, both these estrogenized groups exhibited a reduction in the density of delta-opioid binding in the suprachiasmatic nucleus. Statistically significant changes between either estrogenized groups were not observed for kappa-opioid binding. Results on the hypothalamic concentration of beta-endorphin indicated a marked reduction in EV-injected animals with respect to controls. In contrast, the E2-implanted animals exhibited beta-endorphin concentrations similar to controls. The present results confirm the increase in opioid receptor binding previously reported in the hypothalamus of EV-treated rats and further demonstrate that this increase is confined to the medial preoptic area and exclusively concerns mu-opioid receptors. The concomitant reduction in beta-endorphin levels observed in the same group of animals suggests that the observed increase in mu-opioid binding could reflect a chronic up-regulation of the receptor in response to compromised beta-endorphin input. Given the restriction of this effect to the site of origin of LHRH neurons and the demonstrated inhibitory role of opioids on LHRH release, it is tempting to postulate that such up-regulation could lead to the suppression of the plasma LH pattern that characterizes polycystic ovarian disease in the EV-treated rat.
Desjardins
G C
GC
Montreal Neurological Institute, McGill University, Quebec, Canada.
Beaudet
A
A
Brawer
J R
JR
D000818:Animals; D001345:Autoradiography; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin / Q000378:metabolism; D004343:Drug Implants; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007457:Iodine Radioisotopes; D009928:Organ Specificity; D011085:Polycystic Ovary Syndrome / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D001615:beta-Endorphin / Q000378:metabolism
D004343:Drug Implants; D007457:Iodine Radioisotopes; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D004958:Estradiol; D001615:beta-Endorphin; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin