Modulation of hypothalamic mu-opioid receptor density by estrogen: A quantitative autoradiographic study of the female

The labelling of hypothalamic binding sites by [¹²⁵I]-FK, a specific mu-opioid receptor ligand, was studied in female C57BL/6J mice to test whether removal of ovarian steroids affected the density of distribution of receptor binding. Labelling densities in the forebrain of normally cycling (intact) females (N = 12), were compared to those in mice that had been ovariectomized (OVX) for 6 weeks (n = 8) and in mice that had been OVX and implanted with an estradiol (E2) capsule (OVX+E₂) for 6 weeks (n = 11). Frozen sections from the rostral forebrain were incubated with 1 nM [I25I]-FK and processed for light microscopic autoradiography. The diagonal band of Broca (DBB), organum vasculosum lamina terminalis (OVLT), preoptic area (POA), septum, parietal cortex, and striatum were analyzed using computerized image analysis. The distribution of labelling was similar in all three experimental groups in all the regions; however, labelling was significantly reduced in the ventrolateral POA of OVX animals compared to intact females. Labelling densities in the OVX animals replaced with the gonadal steroid estradiol were not significantly different from those in normally cycling mice. This study demonstrates a region-specific loss of mu-opiate receptor labelling following long-term deprivation of gonadal steroids, and supports the hypothesis that estrogen directly or indirectly influences the density of mu-opioid receptors in the rostral forebrain of female mice.