Estrogen and progesterone modulate [35S]GTPgammaS binding to nociceptin receptors.
Sex steroids modulate reproduction by altering the response of steroid-activated opioid circuits in the hypothalamus and limbic system, by inducing release of endogenous opioids and activation of their cognate receptors. Many studies have concentrated on steroid regulation of exogenous opioid peptides, but steroids also have important actions on opioid receptors inducing receptor trafficking. Opioid receptors are G protein-coupled receptors and their activation catalyzes the exchange of GTP for GDP initiating intracellular signaling cascades. Kinetics of G protein activation were studied using [(35)S]GTPgammaS binding. Catalytic amplification, the number of G proteins activated per occupied receptor, was used as a measure of receptor/transducer amplification. The present study examined whether estrogen and progesterone treatment altered the kinetics of nociceptin opioid receptor (ORL1) in plasma membranes from the medial preoptic area and mediobasal hypothalamus. These hypothalamic regions are important in the gonadal steroid hormone regulation of sexual receptivity. In the mediobasal hypothalamus, estrogen increased ORL1 (B(max)) receptor number 2-fold and maximal GTPgammaS binding (E(max)) 3.9-fold. Subsequent progesterone treatment further increased ORL1 E(max )6.9-fold above baseline, despite a 2-fold decrease in the catalytic amplification factor. In the medial preoptic area, estrogen alone did not increase E(max), but both estrogen and progesterone were able to increase ORL1 B(max) 2.2-fold and E(max) 3-fold, despite having a 3-fold decrease in the catalytic amplification factor. These effects are interesting because they indicate actions of steroids that increase the number of ORL1 but decrease the catalytic amplification suggesting that the steroid effects on opioid receptors are complex and may involve modulation by other signals.
Quesada
Arnulfo
A
Department of Neurobiology, Laboratory of Neuroendocrinology, Brain Research Institute, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095-1763, USA.
Micevych
Paul
P
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000378:metabolism / Q000502:physiology; D011374:Progesterone / Q000494:pharmacology / Q000502:physiology*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D011957:Receptors, Opioid / Q000378:metabolism*; D013462:Sulfur Radioisotopes / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D004967:Estrogens; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011374:Progesterone; D011957:Receptors, Opioid; D013462:Sulfur Radioisotopes; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722285:Oprl1 protein, rat