mu-opioid receptor mRNA expression in identified hypothalamic neurons
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Shi-Xi Zheng1, Martha A Bosch, Oline K Rønnekleiv
1Department of Physiology/Pharmacology, the Oregon Health and Science University, Portland, 97239, USA.
Abstract:
It has been known for a number of years that mu-opioid receptor agonists (e.g., morphine, beta-endorphin, and enkephalin) inhibit luteinizing hormone (LH), vasopressin (VP), and oxytocin (OT) release and stimulate prolactin secretion in rodents and primates by an action at the level of the brain. Also, electrophysiological studies have established that hypothalamic neurons, including gonadotropin-releasing hormone (GnRH), VP, OT, beta-endorphin, and dopamine neurons, are responsive to mu-receptor activation. Although mu-receptor expression has been demonstrated in the hypothalamus, there have been few studies localizing these receptors in neurosecretory neurons. Therefore, we sought to document mu-opioid receptor mRNA expression in immunocytochemically identified hypothalamic neurons. The brains from both female and male guinea pigs were examined by using in situ hybridization and immunocytochemistry. The studies revealed that mu-receptor mRNA was expressed in different diencephalic regions including the preoptic area, the bed nuclei stria terminalis, the paraventricular nucleus thalamus, and the anterior hypothalamus, as well as the supraoptic (SON), paraventricular (PVH), ventromedial, dorsomedial, and arcuate nuclei of the hypothalamus. Importantly, mu-opioid receptors were expressed in subpopulations of GnRH neurons (33.25 +/- 4.6% and 33.6 +/- 3.7% in females and males, respectively), dopamine neurons (51.7 +/- 5.8% to 75.0 +/- 2.6%, depending on neuronal location), beta-endorphin neurons (68.3.0 +/- 4.4%), and VP neurons (41-70%, depending on neuronal location). Because mu-opioid receptors couple via G-proteins to activate inwardly rectifying potassium channels and to inhibit calcium channels, the presence of these receptors is likely to play a major role in directly controlling the excitability of hypothalamic neurons.
Insights
Mu-opioid receptors are present in key hypothalamic neurons controlling hormone release. This finding explains how these receptors directly influence luteinizing hormone, vasopressin, and oxytocin secretion.
Area of Science:
- Neuroendocrinology
- Molecular Neuroscience
- Receptor Pharmacology
Background:
- Mu-opioid receptor agonists are known to modulate the release of hormones like luteinizing hormone (LH), vasopressin (VP), and oxytocin (OT), and affect prolactin secretion.
- Electrophysiological studies confirm that hypothalamic neurons, including those producing gonadotropin-releasing hormone (GnRH), VP, OT, beta-endorphin, and dopamine, respond to mu-opioid receptor activation.
- Previous research indicated mu-opioid receptor presence in the hypothalamus but lacked detailed localization within specific neurosecretory neurons.
Purpose of the Study:
- To investigate and document the expression of mu-opioid receptor mRNA in immunocytochemically identified hypothalamic neurons.
- To precisely map the location of mu-opioid receptors within neurosecretory cell populations in the guinea pig hypothalamus.
Main Methods:
- Utilized in situ hybridization and immunocytochemistry techniques on brain tissue from both male and female guinea pigs.
- Examined various diencephalic and hypothalamic nuclei, including the preoptic area, bed nuclei of the stria terminalis, thalamus, anterior hypothalamus, and specific nuclei like SON, PVH, ventromedial, dorsomedial, and arcuate nuclei.
- Quantified mu-opioid receptor mRNA expression in identified neuronal populations such as GnRH, dopamine, beta-endorphin, and VP neurons.
Main Results:
- Mu-opioid receptor mRNA was detected in multiple diencephalic and hypothalamic regions.
- Significant subpopulations of GnRH (approx. 33%), dopamine (approx. 52-75%), beta-endorphin (approx. 68%), and VP (approx. 41-70%) neurons were found to express mu-opioid receptors.
- Expression levels varied depending on the specific neuronal location and sex.
Conclusions:
- Mu-opioid receptors are expressed in key hypothalamic neurosecretory neurons involved in regulating hormone release.
- The presence of these receptors suggests a direct mechanism by which mu-opioids control the excitability of these neurons.
- This direct control mechanism likely plays a significant role in modulating the release of LH, VP, OT, and prolactin.
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