Neurogenic pain and steroid synthesis in the spinal cord
The spinal cord (SC) is a biosynthetic center for neurosteroids, including pregnenolone (PREG), progesterone (PROG), and 3alpha/5alpha-tetrahydroprogesterone (3alpha/5alpha-THP). In particular, an active form of cytochrome P450 sidechain cleavage (P450scc) has been localized in sensory networks of t...
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| Veröffentlicht in: | Journal of molecular neuroscience 2006, Vol.28 (1), p.17-32 |
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| creator | Patte-Mensah, Christine Kibaly, Cherkaouia Boudard, Domitille Schaeffer, Véronique Béglé, Aurélie Saredi, Simona Meyer, Laurence Mensah-Nyagan, Ayikoe G |
| description | The spinal cord (SC) is a biosynthetic center for neurosteroids, including pregnenolone (PREG), progesterone (PROG), and 3alpha/5alpha-tetrahydroprogesterone (3alpha/5alpha-THP). In particular, an active form of cytochrome P450 sidechain cleavage (P450scc) has been localized in sensory networks of the rat SC dorsal horn (DH). P450scc is the key enzyme catalyzing the conversion of cholesterol (CHOL) into PREG, the rate-limiting step in the biosynthesis of all classes of steroids. To determine whether neurosteroidogenesis might be involved in the pivotal role played by the DH in nociception, effects of neurogenic pain provoked by sciatic nerve ligature were investigated on P450scc expression, cellular distribution, and activity in the SC. P450scc mRNA concentration was threefold higher in the DH of neuropathic rats than in controls. The nerve ligature also increased the density of P450sccpositive neuronal perykarya and fibers in the ipsilateral DH. Incubation of spinal tissue homogenates with [3H]CHOL revealed that the amount of newly synthesized [3H]PREG from [3H]CHOLwas 80% higher in the DH of neuropathic rats. Radioimmunoassays showed an increase of PREG and 3alpha/5alpha-THP concentrations in neuropathic rat DH. The upregulation of PREG and 3alpha/5alpha-THP biosynthesis might be involved in endogenous mechanisms triggered by neuropathic rats to cope with the chronic pain state. 3alpha/5alpha-THP formation from PREG can also generate PROG, which decreases sensitivity to pain and protects nerve cells against degeneration. Because apoptotic cell death has been demonstrated in the DH during neuropathic pain, activation of neurosteroidogenesis in spinal tissues might also be correlated to the neuroprotective role of steroids in the SC. |
| doi_str_mv | 10.1385/jmn:28:1:17 |
| format | Article |
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In particular, an active form of cytochrome P450 sidechain cleavage (P450scc) has been localized in sensory networks of the rat SC dorsal horn (DH). P450scc is the key enzyme catalyzing the conversion of cholesterol (CHOL) into PREG, the rate-limiting step in the biosynthesis of all classes of steroids. To determine whether neurosteroidogenesis might be involved in the pivotal role played by the DH in nociception, effects of neurogenic pain provoked by sciatic nerve ligature were investigated on P450scc expression, cellular distribution, and activity in the SC. P450scc mRNA concentration was threefold higher in the DH of neuropathic rats than in controls. The nerve ligature also increased the density of P450sccpositive neuronal perykarya and fibers in the ipsilateral DH. Incubation of spinal tissue homogenates with [3H]CHOL revealed that the amount of newly synthesized [3H]PREG from [3H]CHOLwas 80% higher in the DH of neuropathic rats. Radioimmunoassays showed an increase of PREG and 3alpha/5alpha-THP concentrations in neuropathic rat DH. The upregulation of PREG and 3alpha/5alpha-THP biosynthesis might be involved in endogenous mechanisms triggered by neuropathic rats to cope with the chronic pain state. 3alpha/5alpha-THP formation from PREG can also generate PROG, which decreases sensitivity to pain and protects nerve cells against degeneration. Because apoptotic cell death has been demonstrated in the DH during neuropathic pain, activation of neurosteroidogenesis in spinal tissues might also be correlated to the neuroprotective role of steroids in the SC.</description><identifier>ISSN: 0895-8696</identifier><identifier>EISSN: 0895-8696</identifier><identifier>EISSN: 1559-1166</identifier><identifier>DOI: 10.1385/jmn:28:1:17</identifier><identifier>PMID: 16632873</identifier><language>eng</language><publisher>United States: Springer Nature B.V</publisher><subject>3-alpha-Hydroxysteroid Dehydrogenase (B-Specific) - metabolism ; 3-Hydroxysteroid Dehydrogenases - metabolism ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase - metabolism ; Animals ; Biosynthesis ; Cholesterol Side-Chain Cleavage Enzyme - metabolism ; Enzymes ; Humans ; Life Sciences ; Ligation ; Neurons - cytology ; Neurons - metabolism ; Neurons and Cognition ; Pain - metabolism ; Pregnenolone - metabolism ; Progesterone - analogs & derivatives ; Progesterone - metabolism ; Rodents ; Sciatic Nerve - surgery ; Spinal Cord - cytology ; Spinal Cord - metabolism ; Steroid 17-alpha-Hydroxylase - metabolism ; Steroids - biosynthesis</subject><ispartof>Journal of molecular neuroscience, 2006, Vol.28 (1), p.17-32</ispartof><rights>Humana Press Inc. 2006</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c487t-c0a1292d482c8c5084cdfc1b0410c9b744c133ae91efd3a926b1740c24823a103</citedby><orcidid>0000-0002-9970-8214 ; 0000-0001-5707-2062</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16632873$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-00092775$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Patte-Mensah, Christine</creatorcontrib><creatorcontrib>Kibaly, Cherkaouia</creatorcontrib><creatorcontrib>Boudard, Domitille</creatorcontrib><creatorcontrib>Schaeffer, Véronique</creatorcontrib><creatorcontrib>Béglé, Aurélie</creatorcontrib><creatorcontrib>Saredi, Simona</creatorcontrib><creatorcontrib>Meyer, Laurence</creatorcontrib><creatorcontrib>Mensah-Nyagan, Ayikoe G</creatorcontrib><title>Neurogenic pain and steroid synthesis in the spinal cord</title><title>Journal of molecular neuroscience</title><addtitle>J Mol Neurosci</addtitle><description>The spinal cord (SC) is a biosynthetic center for neurosteroids, including pregnenolone (PREG), progesterone (PROG), and 3alpha/5alpha-tetrahydroprogesterone (3alpha/5alpha-THP). In particular, an active form of cytochrome P450 sidechain cleavage (P450scc) has been localized in sensory networks of the rat SC dorsal horn (DH). P450scc is the key enzyme catalyzing the conversion of cholesterol (CHOL) into PREG, the rate-limiting step in the biosynthesis of all classes of steroids. To determine whether neurosteroidogenesis might be involved in the pivotal role played by the DH in nociception, effects of neurogenic pain provoked by sciatic nerve ligature were investigated on P450scc expression, cellular distribution, and activity in the SC. P450scc mRNA concentration was threefold higher in the DH of neuropathic rats than in controls. The nerve ligature also increased the density of P450sccpositive neuronal perykarya and fibers in the ipsilateral DH. Incubation of spinal tissue homogenates with [3H]CHOL revealed that the amount of newly synthesized [3H]PREG from [3H]CHOLwas 80% higher in the DH of neuropathic rats. Radioimmunoassays showed an increase of PREG and 3alpha/5alpha-THP concentrations in neuropathic rat DH. The upregulation of PREG and 3alpha/5alpha-THP biosynthesis might be involved in endogenous mechanisms triggered by neuropathic rats to cope with the chronic pain state. 3alpha/5alpha-THP formation from PREG can also generate PROG, which decreases sensitivity to pain and protects nerve cells against degeneration. Because apoptotic cell death has been demonstrated in the DH during neuropathic pain, activation of neurosteroidogenesis in spinal tissues might also be correlated to the neuroprotective role of steroids in the SC.</description><subject>3-alpha-Hydroxysteroid Dehydrogenase (B-Specific) - metabolism</subject><subject>3-Hydroxysteroid Dehydrogenases - metabolism</subject><subject>3-Oxo-5-alpha-Steroid 4-Dehydrogenase - metabolism</subject><subject>Animals</subject><subject>Biosynthesis</subject><subject>Cholesterol Side-Chain Cleavage Enzyme - metabolism</subject><subject>Enzymes</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Ligation</subject><subject>Neurons - cytology</subject><subject>Neurons - metabolism</subject><subject>Neurons and Cognition</subject><subject>Pain - metabolism</subject><subject>Pregnenolone - metabolism</subject><subject>Progesterone - analogs & derivatives</subject><subject>Progesterone - metabolism</subject><subject>Rodents</subject><subject>Sciatic Nerve - 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In particular, an active form of cytochrome P450 sidechain cleavage (P450scc) has been localized in sensory networks of the rat SC dorsal horn (DH). P450scc is the key enzyme catalyzing the conversion of cholesterol (CHOL) into PREG, the rate-limiting step in the biosynthesis of all classes of steroids. To determine whether neurosteroidogenesis might be involved in the pivotal role played by the DH in nociception, effects of neurogenic pain provoked by sciatic nerve ligature were investigated on P450scc expression, cellular distribution, and activity in the SC. P450scc mRNA concentration was threefold higher in the DH of neuropathic rats than in controls. The nerve ligature also increased the density of P450sccpositive neuronal perykarya and fibers in the ipsilateral DH. Incubation of spinal tissue homogenates with [3H]CHOL revealed that the amount of newly synthesized [3H]PREG from [3H]CHOLwas 80% higher in the DH of neuropathic rats. Radioimmunoassays showed an increase of PREG and 3alpha/5alpha-THP concentrations in neuropathic rat DH. The upregulation of PREG and 3alpha/5alpha-THP biosynthesis might be involved in endogenous mechanisms triggered by neuropathic rats to cope with the chronic pain state. 3alpha/5alpha-THP formation from PREG can also generate PROG, which decreases sensitivity to pain and protects nerve cells against degeneration. Because apoptotic cell death has been demonstrated in the DH during neuropathic pain, activation of neurosteroidogenesis in spinal tissues might also be correlated to the neuroprotective role of steroids in the SC.</abstract><cop>United States</cop><pub>Springer Nature B.V</pub><pmid>16632873</pmid><doi>10.1385/jmn:28:1:17</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-9970-8214</orcidid><orcidid>https://orcid.org/0000-0001-5707-2062</orcidid></addata></record> |
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| ispartof | Journal of molecular neuroscience, 2006, Vol.28 (1), p.17-32 |
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| subjects | 3-alpha-Hydroxysteroid Dehydrogenase (B-Specific) - metabolism 3-Hydroxysteroid Dehydrogenases - metabolism 3-Oxo-5-alpha-Steroid 4-Dehydrogenase - metabolism Animals Biosynthesis Cholesterol Side-Chain Cleavage Enzyme - metabolism Enzymes Humans Life Sciences Ligation Neurons - cytology Neurons - metabolism Neurons and Cognition Pain - metabolism Pregnenolone - metabolism Progesterone - analogs & derivatives Progesterone - metabolism Rodents Sciatic Nerve - surgery Spinal Cord - cytology Spinal Cord - metabolism Steroid 17-alpha-Hydroxylase - metabolism Steroids - biosynthesis |
| title | Neurogenic pain and steroid synthesis in the spinal cord |
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