Estrogen Modulation of Opioid and Cholecystokinin Systems in the Limbic-Hypothalamic Circuit

Micevych, Paul E.; Eckersell, Clair B.; Brecha, Nicholas C.; Holland, Krista

doi:10.1016/s0361-9230(97)00212-8

Cited by 50 publications

(31 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2). Within the MPN, ␤-END immunoreactive fibers were distributed in the periventricular preoptic area and the medial MPN , overlapping the distribution of MOR immunoreactivity (Micevych et al, 1997;Eckersell et al, 1998;Sinchak and Micevych, 2001). In the MPN of OVX rats, MOR immunoreactivity was associated with the plasma membrane (Fig.…”

Section: Experiments 1: Do Treatments That Induce Y 1 R Internalizatiomentioning

confidence: 77%

Estrogen-Induced μ-Opioid Receptor Internalization in the Medial Preoptic Nucleus Is Mediated via Neuropeptide Y-Y₁Receptor Activation in the Arcuate Nucleus of Female Rats

Mills¹,

Sohn²,

Micevych³

2004

J. Neurosci.

106

152

View full text Add to dashboard Cite

Section: Experiments 1: Do Treatments That Induce Y 1 R Internalizatiomentioning

confidence: 77%

Estrogen-Induced μ-Opioid Receptor Internalization in the Medial Preoptic Nucleus Is Mediated via Neuropeptide Y-Y₁Receptor Activation in the Arcuate Nucleus of Female Rats

Mills¹,

Sohn²,

Micevych³

2004

J. Neurosci.

106

152

View full text Add to dashboard Cite

“…There are a number of possible molecular mechanisms via which estrogen might diminish OFQ-induced antinociception, including decreasing the expression of the ORL 1 receptor (Flores et al, 2003) and/or its coupling to G-proteins (for review, see Kelly and Wagner, 1999;Malyala et al, 2005), which would secondarily modify the affinity of OFQ to the ORL 1 receptor. Estrogen receptors (ER␣/ER␤) are present in spinal dorsal horn neurons (Amandusson et al, 1996(Amandusson et al, , 1999Shughrue et al, 1997), and estrogen, in addition to altering the expression of opioid peptides (Medina et al, 1993;Micevych et al, 1997;Amandusson et al, 1999;Micevych and Sinchak, 2001) (for review, see Craft et al, 2004), has also been shown by us and others to alter the expression of the ORL 1 receptor gene and protein in the trigeminal region and the hypothalamus (Sinchak et al, 1997;Flores et al, 2003;Sinchak et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Activation of Opioid Receptor Like-1 Receptor in the Spinal Cord Produces Sex-Specific Antinociception in the Rat: Estrogen Attenuates Antinociception in the Female, whereas Testosterone Is Required for the Expression of Antinociception in the Male

Claiborne¹,

Nag²,

Mokha³

2006

J. Neurosci.

View full text Add to dashboard Cite

Sex-related differences in the perception and modulation of pain have been reported. The present study is the first to investigate systematically whether activation of opioid receptor-like 1 receptor (ORL 1 ) by orphanin FQ (OFQ) produces sex-specific modulation of spinal nociception and whether estrogen or testosterone contributes to these differences using the rat as an experimental animal. Two behavioral models, the NMDA and heat-induced nociceptive tests, were used to examine sex-specific modulation of spinal nociception. Intrathecal microinjection of OFQ in male, ovariectomized (OVX), and diestrous rats produced a significant antinociceptive effect on both tests. However, OFQ failed to produce antinociception in proestrous rats, the phase of the estrous cycle with the highest levels of circulating estradiol, and produced a dose-dependent effect in OVX females treated with 1 ng to 100 g of estradiol. The antinociceptive effects of OFQ were dose dependent in male and OVX animals and were reversibly antagonized by UFP-101 ([Nphe 1 ,Arg ,Lys 15]N/ OFQ(1-13)-NH 2 ), an ORL 1 receptor-selective antagonist. Interestingly, OFQ was ineffective in gonadectomized (GDX) males, whereas testosterone replacement restored the antinociceptive effect of OFQ in GDX males. We conclude that OFQ produces sex-specific modulation of spinal nociception; estrogen attenuates antinociception in the female in parallel with normal cycling of estrogen levels, and testosterone is required for the expression of antinociception in the male; thus, the sensitivity of the male to the antinociceptive effects of OFQ is not simply attributable to the intrinsically low estrogen levels in these animals.

show abstract

“…There are several potential candidates in the limbic-hypothalamic circuit. Estrogen increases the expression of the enkephalin precursor preproenkephalin mRNA in the MPNm, MeApd, and ventromedial hypothalamus (Romano et al, 1989;Eckersell et al, 1994;Priest et al, 1995;Holland et al, 1997). Furthermore, the immunocytochemical distribution of ␤-endorphin increases on estrus, the day after estrogen levels peak during the estrous cycle (Ge et al, 1993), and ␤-endorphin fiber density in the MPNm varies with sex steroid levels (Hammer and Cheung, 1995).…”

Section: Discussionmentioning

confidence: 99%

Estrogen-Induced Alteration of μ-Opioid Receptor Immunoreactivity in the Medial Preoptic Nucleus and Medial Amygdala

1998

Self Cite

View full text Add to dashboard Cite

The -opioid receptor ( -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 -OR internalization in response to natural stimuli. In this study, we used laser-scanning microscopy to demonstrate that estrogen treatment induces the translocation of -OR immunoreactivity ( -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 -ORi at the bright-field light microscopic level. In the absence of stimulation, the majority of immunoreactivity is diffuse, with few definable -ORϩ cell bodies or processes. After stimulation, the density of distinct processes filled with -ORi was significantly increased. We interpreted the increase in the number of -ORϩ processes as indicating increased levels of internalization. Using this increase in the density of -ORϩ 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 Ͼ24 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 -ORϩ processes. These data imply that estrogen treatment stimulates the release of endogenous opioids that activate -OR in the limbic system and hypothalamus providing a "neurochemical signature" of steroid activation of these circuits.

show abstract

Estrogen Modulation of Opioid and Cholecystokinin Systems in the Limbic-Hypothalamic Circuit

Cited by 50 publications

References 75 publications

Estrogen-Induced μ-Opioid Receptor Internalization in the Medial Preoptic Nucleus Is Mediated via Neuropeptide Y-Y₁Receptor Activation in the Arcuate Nucleus of Female Rats

Estrogen-Induced μ-Opioid Receptor Internalization in the Medial Preoptic Nucleus Is Mediated via Neuropeptide Y-Y₁Receptor Activation in the Arcuate Nucleus of Female Rats

Activation of Opioid Receptor Like-1 Receptor in the Spinal Cord Produces Sex-Specific Antinociception in the Rat: Estrogen Attenuates Antinociception in the Female, whereas Testosterone Is Required for the Expression of Antinociception in the Male

Estrogen-Induced Alteration of μ-Opioid Receptor Immunoreactivity in the Medial Preoptic Nucleus and Medial Amygdala

Contact Info

Product

Resources

About

Estrogen Modulation of Opioid and Cholecystokinin Systems in the Limbic-Hypothalamic Circuit

Cited by 50 publications

References 75 publications

Estrogen-Induced μ-Opioid Receptor Internalization in the Medial Preoptic Nucleus Is Mediated via Neuropeptide Y-Y1Receptor Activation in the Arcuate Nucleus of Female Rats

Estrogen-Induced μ-Opioid Receptor Internalization in the Medial Preoptic Nucleus Is Mediated via Neuropeptide Y-Y1Receptor Activation in the Arcuate Nucleus of Female Rats

Activation of Opioid Receptor Like-1 Receptor in the Spinal Cord Produces Sex-Specific Antinociception in the Rat: Estrogen Attenuates Antinociception in the Female, whereas Testosterone Is Required for the Expression of Antinociception in the Male

Estrogen-Induced Alteration of μ-Opioid Receptor Immunoreactivity in the Medial Preoptic Nucleus and Medial Amygdala

Contact Info

Product

Resources

About

Estrogen-Induced μ-Opioid Receptor Internalization in the Medial Preoptic Nucleus Is Mediated via Neuropeptide Y-Y₁Receptor Activation in the Arcuate Nucleus of Female Rats

Estrogen-Induced μ-Opioid Receptor Internalization in the Medial Preoptic Nucleus Is Mediated via Neuropeptide Y-Y₁Receptor Activation in the Arcuate Nucleus of Female Rats