EFFECTS OF OVARIAN-STEROIDS ON HYPOTHALAMIC OPIOID RECEPTOR SUBTYPES IN OVARIECTOMIZED EWES - REGIONAL CHANGES IN DENSITY AND AFFINITY

The negative feedback regulation by ovarian steroids of luteinizing hormone secretion may be partially mediated by a hypothalamic endogenous opioid mechanism. This could be affected by ovarian steroid-regulated changes in hypothalamic opioid receptor binding mechanisms. In this report we show that in the presence of blocking concentrations of site-selective opioid analogues, [H-3]diprenorphin homogeneously labelled mu, delta or kappa receptor subtypes respectively. Using this receptor binding model, we characterized each opioid receptor subtype in the hypothalamic preoptic area and medio-basal hypothalamus of ovariectomized (OVX) and OVX plus progesterone- or oestradiol-17 beta (OE(2))-treated ewes. In the preoptic area, progesterone treatment did not influence the affinity or capacity of delta or kappa receptor binding sites, but significantly reduced mu receptor subtype content (20% less than control) with no statistically significant change in affinity. There was no effect of OE(2) on either the affinity or capacity of each opioid receptor subtype in this area. In the mediobasal hypothalamus, progesterone treatment significantly decreased delta subtype receptor affinity (22 +/- 11 nM vs control 7 +/- 2 nM) and increased binding capacity (78 +/- 9 fmol/mg protein vs control 37 +/- 16 fmol/mg protein). OE(2) treatment had a similar, though more profound effect on affinity (51 +/- 17 nM) and binding capacity (139 +/- 26 fmol/mg protein) at the delta receptor binding site. There were no significant changes in the affinity or capacity of mu or kappa binding sites in the medio-basal hypothalamus. These results indicate that steroid hormones modulate hypothalamic opioid receptors in the OVX ewe in a receptor subtype- and region-dependent manner. The precise role of these steroid-induced changes in opioid receptor characteristics remains to be determined.