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The Journal of Neuroscience, May 15, 1998, 18(10):3967-3976
Estrogen-Induced Alteration of µ-Opioid Receptor Immunoreactivity in the Medial Preoptic Nucleus and Medial Amygdala
Clair B. Eckersell , Paul Popper , and Paul E Micevych Department of Neurobiology, School of Medicine, and the Laboratory of Neuroendocrinology, Brain Research Institute, University of California Los Angeles, Los Angeles, California 90095-1763
The µ-opioid receptor (µ-OR), like most G-protein-coupled receptors, is rapidly internalized after agonist binding. Although opioid peptides induce internalization in vivo, there are no studies that demonstrate µ-OR internalization in response to natural stimuli. In this study, we used laser-scanning microscopy to demonstrate that estrogen treatment induces the translocation of µ-OR immunoreactivity (µ-ORi) from the membrane to an internal location in steroid-sensitive cell groups of the limbic system and hypothalamus. Estrogen-induced internalization was prevented by the opioid antagonist naltrexone, suggesting that translocation was largely dependent on release of endogenous agonists. Estrogen treatment also altered the pattern of µ-ORi at the bright-field light microscopic level. In the absence of stimulation, the majority of immunoreactivity is diffuse, with few definable µ-OR+ cell bodies or processes. After stimulation, the density of distinct processes filled with µ-ORi was significantly increased. We interpreted the increase in the number of µ-OR+ processes as indicating increased levels of internalization. Using this increase in the density of µ-OR+ fibers, we showed that treatment of ovariectomized rats with estradiol benzoate induced a rapid and reversible increase in the number of fibers. Significant internalization was noted within 30 min and lasted for >24 hr after estrogen treatment in the medial preoptic nucleus, the principal part of the bed nucleus, and the posterodorsal medial amygdala. Naltrexone prevented the increase of µ-OR+ processes. These data imply that estrogen treatment stimulates the release of endogenous opioids that activate µ-OR in the limbic system and hypothalamus providing a "neurochemical signature" of steroid activation of these circuits.
Key words: receptor internalization; neurochemistry of reproduction; steroid hormones; opioid peptides; G-protein-coupled receptors; hypothalamus
Copyright © 1998 Society for Neuroscience 0270-6474/98/18103967-10$05.00/0
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