Effects of ovarian hormones on brain opioid binding sites in castrated female rats

Dondi, D.; Limonta, Patrizia; Maggi, Roberto; Piva, F.

doi:10.1152/ajpendo.1992.263.3.e507

Cited by 14 publications

(25 citation statements)

References 29 publications

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“…Since some effects of androgens are medi- ated by their conversion to estradiol [20,45], further work will be required to determine their actual pain modulation by using aromatase inhibitors to prevent the conversion of testosterone to estradiol. Evidence has shown that estradiol administration to OVX rats increases μ-opioid receptor protein in the hypothalamus [46][47][48] and enkephalin mRNA expression [49], indicating that estrogen can induce an increase in endogenous antinociception and thus reduce pain sensitivity. The P2X 3 receptor subtype has been found to be involved in peripheral pain signal transduction [26,[50][51][52][53].…”

Section: Discussionmentioning

confidence: 99%

Estrogen modulation of peripheral pain signal transduction: involvement of P2X3 receptors

Jin

et al. 2011

Purinergic Signalling

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There is evidence that gonadal hormones may affect the perception of painful stimulation, although the underlying mechanisms remain unclear. This investigation was undertaken to determine whether the adenosine 5′-triphosphate (ATP) receptor subunit, P2X 3 , is involved in the modulatory action of estrogen in peripheral pain signal transduction in dorsal root ganglion (DRG). The mechanical pain behavior test, real-time quantitative reverse transcription-polymerase chain reaction analysis, and Western blot methods were used to determine the mean relative concentrations and functions of P2X 3 receptors in DRG in sham, ovariectomized (OVX), and estradiol replacement (OVX+E 2 ) female rats and in sham and orchiectomized male rats. The mechanical hyperalgesia appeared after ovariectomy, which was subsequently reversed after estradiol replacement, whereas it was not observed after orchiectomy in male rats. Plantar injection of 2′(3′)-O-(2,4,6-trinitrophenyl) ATP (TNP-ATP), a P2X 3 and P2X 2/3 receptor antagonist, resulted in an increase of the pain threshold force in OVX rats while had no effect on sham rats. Furthermore, A-317491, a selective P2X 3 /P2X 2/3 receptor antagonist, significantly reversed the hyperalgesia of OVX rats. Injection of ATP into the plantars also caused a significant increase of the paw withdrawal duration in OVX rats compared with that seen in the sham group, which became substantially attenuated by TNP-ATP. P2X 3 receptors expressed in DRG were significantly increased in both mRNA and protein levels after ovariectomy and then reversed after estrogen replacement, while a similar increase was not observed after orchiectomy in male rats. Furthermore, P2X 3 mRNA was significantly decreased 24 h after the application of 17β-estradiol in a concentrationdependent manner in cultured DRG neurons. ICI 182,780, an estrogen receptor antagonist, blocked the reduction in the protein level. These results suggest that the female gonadal hormone, 17β-estradiol, might participate in the control of peripheral pain signal transduction by modulating P2X 3 receptor-mediated events in primary sensory neurons, probably through genomic mechanisms.

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Section: Discussionmentioning

confidence: 99%

Estrogen modulation of peripheral pain signal transduction: involvement of P2X3 receptors

Jin

et al. 2011

Purinergic Signalling

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“…Progesterone and Opioid Interaction possible target of sex steroids. Recently, Dondi et al [21] demonstrated that estradiol treat ment increased the number of p-binding sites in the hippocampus and in the thalamus but not in the hypothalamus. After acute estradiol plus progesterone treatment, there was a significant increase in hypothalamic P-endorphin levels.…”

Section: Discussionmentioning

confidence: 99%

Diurnal Variation in the Acute Effects of Estradiol and Progesterone on Beta-Endorphin and Met-Enkephalin Levels in Specific Brain Regions of Ovariectomized Rats

Gordon¹,

Soliman²

1994

Pharmacology

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The present investigation was conducted to evaluate the effects of estradiol and progesterone on β-endorphin and Met-enkephalin levels in specific brain regions of ovariectomized rats. Female Sprague-Dawley rats (100-120 g) adapted to a 12-hour light, 12-hour dark illumination cycle were used in these studies. Animals were ovariectomized under pentobarbital anesthesia. After a recovery period of 10-14 days, estradiol (50 µg/kg in 0.2 ml olive oil) was administered subcutaneously to rats at either 8.00, 14.00 or 16.00 h, progesterone (5 mg/kg in 0.1 ml olive oil) or estradiol plus progesterone was administered subcutaneously at 16.00 h. Control rats were injected with olive oil. Animals were sacrificed 2 h later. The cerebral cortex, hypothalamus, hippocampus and midbrain were dissected, and their β-endorphin and Met-enkephalin levels were determined by radioimmunoassay. Estradiol administration at 8.00 h resulted in a significant decline in β-endorphin levels of the hippocampus (66% decrease) and a significant rise in Met-enkephalin levels of the hypothalamus (37.8% increase) but had no effect on other brain regions studied. When estradiol was administered at 14.00 h, it produced a significant change in β-endorphin levels in the cerebral cortex (34.7% increase) and in the mid-brain (31.3% increase), but these levels were not altered in the other brain regions. At 16.00 h estradiol and progesterone alone caused a significant increase (29 and 43%, respectively) in β-endorphin levels of the hippocampus. Similarly, the Met-enkephalin levels in the hippocampus significantly increased following administration of estradiol (57% increase) and progesterone (54% increase) alone. However, estradiol and progesterone administered in combination produced a significant change in β-endorphin levels in the hypothalamus (25% increase) and in the cerebral cortex (30% increase). Moreover, the Met-enkephalin levels in the cerebral cortex significantly increased with all treatments whereas these levels in the mid-brain increased only when estradiol and progesterone were administered in combination. These findings indicate that estradiol and progesterone affect β-endorphin as well as Met-enkephalin levels in specific brain regions and that these effects are diurnally controlled. In addition, the alteration in hippocampal endogenous opioid levels induced by estrogen and progesterone may in part explain their behavioral effects.

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“…LIGAND and DESIGN computer pro grams were used, respectively, to analyze the ligand-binding data and to optimize the experimental protocols. A detailed description of these programs can be found in previous reports [25,26]. The LIGAND program was used to analyze simultaneously the five homologous inhibition curves arising from each experimental group, in order to estimate the binding parameters (Bmax and Kd) represen tative for each group.…”

Section: Statistical a Nalysismentioning

confidence: 99%

Binding Characteristics of Hypothalamic Mu Opioid Receptors throughout the Estrous Cycle in the Rat

Maggi

Dondi²,

Rovati³

et al. 1993

Neuroendocrinology

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This study presents a detailed analysis of the binding characteristics of hypothalamic mu opioid receptors during the different phases of the estrous cycle of the female rat. Different groups of adult female rats with a regular 4-day estrous cycle were killed by decapitation at 10.00 h of diestrus days 1 and 2, at 10.00, 12.00, 14.00, 16.00, 18.00 and 20.00 h of the day of proestrus and at 10.00, 12.00, 14.00, 16.00 and 18.00 h of the day of estrus. At sacrifice, the hypothalami of the animals were dissected out, plasma membrane preparations were obtained and the binding characteristics (Bmax, Kd) of the specific mu opioid ligand dihydromorphine (DHM) on mu opioid receptors were evaluated. Blood has been collected from the trunk vessels to monitor with specific radioimmunoassays serum levels of LH, estradiol and progesterone. The data obtained indicate that in the hypothalamus of female rats with a regular 4-day estrous cycle, the binding characteristics of DHM for mu receptors show important variations during the different phases of the estrous cycle. In general, the number of mu opioid receptors is elevated during the morning of diestrus day 2 and during the day of proestrus being maximal at 14.00 h and declining significantly at 18.00 and 20.00 h of the same day. At estrus, the number of mu receptors appears high at 10.00 and 16.00 h and low at 12.00, 14.00 and 18.00 h. All these variations take place without any significant change of the affinity (Kd) of DHM for the mu receptors. The lowest density of mu receptors was recorded at 10.00 h of the first day of diestrus, but this occurred in the presence of a significant decrease of the Kd (i.e., of an increase of affinity) of the ligand for the mu receptors. The decrease of the number of mu receptors observed in the afternoon of proestrus coincides with the beginning of the LH surge and might be linked to the increase of serum levels of estradiol and progesterone, which is apparent during this phase of the estrous cycle, these findings agree with the hypothesis that the positive feedback effect exerted by estrogens plus progesterone on LH release is also realized through a disinhibition of the opiatergic tone impinging on the hypothalamus.

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Effects of ovarian hormones on brain opioid binding sites in castrated female rats

Cited by 14 publications

References 29 publications

Estrogen modulation of peripheral pain signal transduction: involvement of P2X3 receptors

Estrogen modulation of peripheral pain signal transduction: involvement of P2X3 receptors

Diurnal Variation in the Acute Effects of Estradiol and Progesterone on Beta-Endorphin and Met-Enkephalin Levels in Specific Brain Regions of Ovariectomized Rats

Binding Characteristics of Hypothalamic Mu Opioid Receptors throughout the Estrous Cycle in the Rat

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