pregnanolone

Summary

Summary: A pregnane found in the urine of pregnant women and sows. It has anesthetic, hypnotic, and sedative properties.

Top Publications

  1. Uzunova V, Sampson L, Uzunov D. Relevance of endogenous 3alpha-reduced neurosteroids to depression and antidepressant action. Psychopharmacology (Berl). 2006;186:351-61 pubmed
    The naturally occurring 3alpha-reduced neurosteroids allopregnanolone and its isomer pregnanolone are among the most potent positive allosteric modulators of gamma-aminobutyric acid type A receptors...
  2. Kussius C, Kaur N, Popescu G. Pregnanolone sulfate promotes desensitization of activated NMDA receptors. J Neurosci. 2009;29:6819-27 pubmed publisher
    ..b>Pregnanolone sulfate (PAS) is an endogenous neurosteroid that inhibits NMDA receptors and is neuroprotective in vivo...
  3. Smith C, Wekstein D, Markesbery W, Frye C. 3alpha,5alpha-THP: a potential plasma neurosteroid biomarker in Alzheimer's disease and perhaps non-Alzheimer's dementia. Psychopharmacology (Berl). 2006;186:481-5 pubmed
    ..Lowered 3alpha,5alpha-THP levels appear promising as a biomarker in dementia, but further work is needed to establish the sensitivity and specificity of these findings in AD. ..
  4. Gurkovskaya O, Leonard S, Lewis P, Winsauer P. Effects of pregnanolone and dehydroepiandrosterone on ethanol intake in rats administered ethanol or saline during adolescence. Alcohol Clin Exp Res. 2009;33:1252-64 pubmed publisher
    ..Following these manipulations, pregnanolone (1 to 10 mg/kg) and dehydroepiandrosterone (DHEA, 1 to 100 mg/kg) were administered prior to preference ..
  5. Davidson C, Ali N, Micsenyi M, Stephney G, Renault S, Dobrenis K, et al. Chronic cyclodextrin treatment of murine Niemann-Pick C disease ameliorates neuronal cholesterol and glycosphingolipid storage and disease progression. PLoS ONE. 2009;4:e6951 pubmed publisher
    ..Understanding the mechanism(s) by which CD leads to reduced neuronal storage may provide important new opportunities for treatment of NPC and related neurodegenerative diseases characterized by cholesterol dyshomeostasis. ..
  6. Liu B, Li H, Repa J, Turley S, Dietschy J. Genetic variations and treatments that affect the lifespan of the NPC1 mouse. J Lipid Res. 2008;49:663-9 pubmed
    ..It is currently not clear which of these effects is nonspecific or which might relate directly to the molecular defect present in the NPC1 syndrome. ..
  7. Charalampopoulos I, Alexaki V, Tsatsanis C, Minas V, Dermitzaki E, Lasaridis I, et al. Neurosteroids as endogenous inhibitors of neuronal cell apoptosis in aging. Ann N Y Acad Sci. 2006;1088:139-52 pubmed
    ..These findings suggest that neurosteroids may act as endogenous neuroprotective factors. The decline of neurosteroid levels during aging may leave the brain unprotected against neurotoxic challenges. ..
  8. Ossewaarde L, Hermans E, van Wingen G, Kooijman S, Johansson I, Backstrom T, et al. Neural mechanisms underlying changes in stress-sensitivity across the menstrual cycle. Psychoneuroendocrinology. 2010;35:47-55 pubmed publisher
    ..These results provide potential insights into how fluctuations in allopregnanolone that naturally occur during the menstrual cycle may change stress vulnerability. ..
  9. Jiang P, Yang C, Wang Y, Xu T. Mechanisms of modulation of pregnanolone on glycinergic response in cultured spinal dorsal horn neurons of rat. Neuroscience. 2006;141:2041-50 pubmed
    ..However, the modulatory effects of neurosteroid pregnanolone (5beta-pregnan-3alpha-ol-20-one) on native glycine receptors remain unclear...

More Information

Publications62

  1. Hardoy M, Serra M, Carta M, Contu P, Pisu M, Biggio G. Increased neuroactive steroid concentrations in women with bipolar disorder or major depressive disorder. J Clin Psychopharmacol. 2006;26:379-84 pubmed
    ..These differences did not seem to be attributable simply to drug treatment or to comorbidity with other psychiatric conditions in the patients. ..
  2. Hosie A, Wilkins M, Da Silva H, Smart T. Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites. Nature. 2006;444:486-9 pubmed
  3. Ahmad I, Lope Piedrafita S, Bi X, Hicks C, Yao Y, Yu C, et al. Allopregnanolone treatment, both as a single injection or repetitively, delays demyelination and enhances survival of Niemann-Pick C mice. J Neurosci Res. 2005;82:811-21 pubmed
    ..We conclude that allopregnanolone treatment significantly ameliorates several symptoms of NPC in Npc1(-/-) mice, presumably by effects on myelination or neuronal connectivity. ..
  4. Wang J, Irwin R, Liu L, Chen S, Brinton R. Regeneration in a degenerating brain: potential of allopregnanolone as a neuroregenerative agent. Curr Alzheimer Res. 2007;4:510-7 pubmed
    ..Together the data indicate that APalpha may maintain the regenerative ability of the brain and modify progression of AD related pathology. Challenges for efficacy of regenerative agents within a degenerative milieu are discussed. ..
  5. Andreen L, Spigset O, Andersson A, Nyberg S, Backstrom T. Pharmacokinetics of progesterone and its metabolites allopregnanolone and pregnanolone after oral administration of low-dose progesterone. Maturitas. 2006;54:238-44 pubmed
    To investigate the pharmacokinetics of progesterone, allopregnanolone and pregnanolone after treatment with a low oral dose of progesterone...
  6. Sayeed I, Guo Q, Hoffman S, Stein D. Allopregnanolone, a progesterone metabolite, is more effective than progesterone in reducing cortical infarct volume after transient middle cerebral artery occlusion. Ann Emerg Med. 2006;47:381-9 pubmed
    ..Our results suggest that both neurosteroids should be examined for safety and efficacy in a clinical trial for ischemic stroke. ..
  7. Hill M, Cibula D, Havlikova H, Kancheva L, Fait T, Kancheva R, et al. Circulating levels of pregnanolone isomers during the third trimester of human pregnancy. J Steroid Biochem Mol Biol. 2007;105:166-75 pubmed
    This study addresses the question of whether changes in the biosynthesis and metabolism of neuroactive pregnanolone isomers (PIs) might participate in the timing of parturition in humans...
  8. Wang J, Liu L, Irwin R, Chen S, Brinton R. Regenerative potential of allopregnanolone. Brain Res Rev. 2008;57:398-409 pubmed
    ..This review summarizes current APalpha research in different animal models, neural progenitor regeneration within a degenerative milieu and the challenge for developing neuroregenerative therapeutics. ..
  9. Havlikova H, Hill M, Kancheva L, Vrbikova J, Pouzar V, Cerny I, et al. Serum profiles of free and conjugated neuroactive pregnanolone isomers in nonpregnant women of fertile age. J Clin Endocrinol Metab. 2006;91:3092-9 pubmed
    b>Pregnanolone isomers (PI) with a hydroxy group in the 3alpha-position are neuroinhibitors operating via positive modulation of GABA(A) receptors. The 3beta-PI and sulfates of PI and pregnenolone exert the opposite effect...
  10. Wang J, Brinton R. Allopregnanolone-induced rise in intracellular calcium in embryonic hippocampal neurons parallels their proliferative potential. BMC Neurosci. 2008;9 Suppl 2:S11 pubmed publisher
    ..These data suggest that APalpha-induced intracellular calcium concentration increase serves as the initiation mechanism whereby APalpha promotes neurogenesis. ..
  11. Naylor J, Kilts J, Hulette C, Steffens D, Blazer D, Ervin J, et al. Allopregnanolone levels are reduced in temporal cortex in patients with Alzheimer's disease compared to cognitively intact control subjects. Biochim Biophys Acta. 2010;1801:951-9 pubmed publisher
    ..In addition, the APOE4 allele is associated with reduced allopregnanolone levels. Neurosteroids may be relevant to the neurobiology and therapeutics of AD. ..
  12. Wang J, Singh C, Liu L, Irwin R, Chen S, Chung E, et al. Allopregnanolone reverses neurogenic and cognitive deficits in mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A. 2010;107:6498-503 pubmed publisher
  13. Chen S, Wang J, Irwin R, Yao J, Liu L, Brinton R. Allopregnanolone promotes regeneration and reduces β-amyloid burden in a preclinical model of Alzheimer's disease. PLoS ONE. 2011;6:e24293 pubmed publisher
  14. Marx C, Trost W, Shampine L, Stevens R, Hulette C, Steffens D, et al. The neurosteroid allopregnanolone is reduced in prefrontal cortex in Alzheimer's disease. Biol Psychiatry. 2006;60:1287-94 pubmed
    ..01). Subjects with AD demonstrate significant reductions in PFC allopregnanolone levels, a finding that may be relevant to neuropathological disease stage severity. Neurosteroids may have utility as candidate biomarkers in AD. ..
  15. Agis Balboa R, Pinna G, Zhubi A, Maloku E, Veldic M, Costa E, et al. Characterization of brain neurons that express enzymes mediating neurosteroid biosynthesis. Proc Natl Acad Sci U S A. 2006;103:14602-7 pubmed
  16. Langmade S, Gale S, Frolov A, Mohri I, Suzuki K, Mellon S, et al. Pregnane X receptor (PXR) activation: a mechanism for neuroprotection in a mouse model of Niemann-Pick C disease. Proc Natl Acad Sci U S A. 2006;103:13807-12 pubmed
    ..These findings suggest that treatment with pregnane X receptor ligands may be useful clinically in delaying the progressive neurodegeneration in human NPC disease. ..
  17. Shannon E, Purdy R, Grant K. Discriminative stimulus effects of 5.6 mg/kg pregnanolone in DBA/2J and C57BL/6J inbred mice. Alcohol. 2005;37:35-45 pubmed
    ..Two neurosteroids, allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one) and pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one), possess anxiolytic and sedative properties and show substitution for ..
  18. Mellon S, Gong W, Schonemann M. Endogenous and synthetic neurosteroids in treatment of Niemann-Pick Type C disease. Brain Res Rev. 2008;57:410-20 pubmed
    ..These animal models further establish the wide range of functions of these compounds, which may ultimately be useful for treatment of human diseases. ..
  19. Follesa P, Concas A, Porcu P, Sanna E, Serra M, Mostallino M, et al. Role of allopregnanolone in regulation of GABA(A) receptor plasticity during long-term exposure to and withdrawal from progesterone. Brain Res Brain Res Rev. 2001;37:81-90 pubmed
  20. Pluchino N, Genazzani A, Bernardi F, Casarosa E, Pieri M, Palumbo M, et al. Tibolone, transdermal estradiol or oral estrogen-progestin therapies: effects on circulating allopregnanolone, cortisol and dehydroepiandrosterone levels. Gynecol Endocrinol. 2005;20:144-9 pubmed
    ..Unlike estrogen-based therapy, tibolone treatment did not reduce the DHEA milieu in the menopause, and thus did not enhance the androgen deficiency syndrome in postmenopausal women. ..
  21. Bernardi F, Pluchino N, Begliuomini S, Lenzi E, Palumbo M, Luisi M, et al. Disadaptive disorders in women: allopregnanolone, a sensitive steroid. Gynecol Endocrinol. 2004;19:344-53 pubmed
  22. Söderpalm A, Lindsey S, Purdy R, Hauger R, Wit d. Administration of progesterone produces mild sedative-like effects in men and women. Psychoneuroendocrinology. 2004;29:339-54 pubmed
    ..These results suggest that, although the effects are modest and not simply related to plasma concentrations, progesterone and its metabolites can produce sedative-like effects in both men and women. ..
  23. Gomez C, Saldívar González A, Delgado G, Rodriguez R. Rapid anxiolytic activity of progesterone and pregnanolone in male rats. Pharmacol Biochem Behav. 2002;72:543-50 pubmed
    The effect of different doses of progesterone (1.0, 3.0, 10.0, 30.0, and 100.0 mg/kg) and pregnanolone (1.0, 3.0, 10.0, and 30...
  24. Nguyen P, Yan E, Castillo Melendez M, Walker D, Hirst J. Increased allopregnanolone levels in the fetal sheep brain following umbilical cord occlusion. J Physiol. 2004;560:593-602 pubmed
    ..The action of the increased neurosteroid content at GABAA receptors may serve to diminish the increased excitation due to excitotoxic amino acid release, and provide short-term protection to brain cells during such stress. ..
  25. Stoffel Wagner B, Watzka M, Steckelbroeck S, Ludwig M, Clusmann H, Bidlingmaier F, et al. Allopregnanolone serum levels and expression of 5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase isoforms in hippocampal and temporal cortex of patients with epilepsy. Epilepsy Res. 2003;54:11-9 pubmed
    ..These findings provide further molecular biological evidence for the formation and metabolism of neuroactive steroids in the human brain. ..
  26. Serra M, Pisul M, Dazzi L, Purdy R, Biggio G. Prevention of the stress-induced increase in the concentration of neuroactive steroids in rat brain by long-term administration of mirtazapine but not of fluoxetine. J Psychopharmacol. 2002;16:133-8 pubmed
  27. Pearson Murphy B, Allison C. Determination of progesterone and some of its neuroactive ring A-reduced metabolites in human serum. J Steroid Biochem Mol Biol. 2000;74:137-42 pubmed
    ..5alpha-Dihydroprogesterone and 3alpha,5alpha-tetrahydroprogesterone rose substantially in the luteal phase of the menstrual cycle and all rose considerably during pregnancy. ..
  28. Nguyen P, Ross Young I, Walker D, Hirst J. Allopregnanolone in the brain and blood after disruption of the hypothalamic-pituitary-adrenal axis in fetal sheep. J Endocrinol. 2004;182:81-8 pubmed
    ..Thus local control mechanisms within the brain may be responsible for maintaining the high neurosteroid content present during fetal life, as these mechanisms are independent of adrenal steroid production. ..
  29. Zhu D, Wang M, Backstrom T, Wahlstrom G. Evaluation and comparison of the pharmacokinetic and pharmacodynamic properties of allopregnanolone and pregnanolone at induction of anaesthesia in the male rat. Br J Anaesth. 2001;86:403-12 pubmed
    We have evaluated and compared the pharmacokinetic and pharmacodynamic properties of allopregnanolone and pregnanolone at induction of anaesthesia in male rats...
  30. Djebaili M, Guo Q, Pettus E, Hoffman S, Stein D. The neurosteroids progesterone and allopregnanolone reduce cell death, gliosis, and functional deficits after traumatic brain injury in rats. J Neurotrauma. 2005;22:106-18 pubmed
  31. Hill M, Bicikova M, Pařízek A, Havlikova H, Klak J, Fajt T, et al. Neuroactive steroids, their precursors and polar conjugates during parturition and postpartum in maternal blood: 2. Time profiles of pregnanolone isomers. J Steroid Biochem Mol Biol. 2001;78:51-7 pubmed
    Time profiles of the pregnanolone isomers epipregnanolone (3 beta-hydroxy-5 beta-pregnan-20-one), allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one), pregnanolone (3 alpha-hydroxy-5 beta-pregnan-20-one), and isopregnanolone (3 beta-..
  32. Pinna G, Dong E, Matsumoto K, Costa E, Guidotti A. In socially isolated mice, the reversal of brain allopregnanolone down-regulation mediates the anti-aggressive action of fluoxetine. Proc Natl Acad Sci U S A. 2003;100:2035-40 pubmed
    ..We conclude that Allo brain content normalization is a better candidate than 5-HT reuptake inhibition to explain the reduction of aggressiveness elicited by S-FLX and S-NFLX. ..
  33. Covey D, Nathan D, Kalkbrenner M, Nilsson K, Hu Y, Zorumski C, et al. Enantioselectivity of pregnanolone-induced gamma-aminobutyric acid(A) receptor modulation and anesthesia. J Pharmacol Exp Ther. 2000;293:1009-16 pubmed
  34. Follesa P, Serra M, Cagetti E, Pisu M, Porta S, Floris S, et al. Allopregnanolone synthesis in cerebellar granule cells: roles in regulation of GABA(A) receptor expression and function during progesterone treatment and withdrawal. Mol Pharmacol. 2000;57:1262-70 pubmed
    ..Prevention of allopregnanolone synthesis by the 5alpha-reductase inhibitor finasteride also prevented the changes in both GABA(A) receptor gene expression and receptor function elicited by progesterone treatment and withdrawal. ..
  35. Khisti R, Chopde C. Serotonergic agents modulate antidepressant-like effect of the neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one in mice. Brain Res. 2000;865:291-300 pubmed
  36. Darbandi Tonkabon R, Hastings W, Zeng C, Akk G, Manion B, Bracamontes J, et al. Photoaffinity labeling with a neuroactive steroid analogue. 6-azi-pregnanolone labels voltage-dependent anion channel-1 in rat brain. J Biol Chem. 2003;278:13196-206 pubmed
    ..These data suggest that neuroactive steroid effects on the GABA(A) receptor may be mediated by binding to an accessory protein, VDAC-1. ..
  37. Follesa P, Porcu P, Sogliano C, Cinus M, Biggio F, Mancuso L, et al. Changes in GABAA receptor gamma 2 subunit gene expression induced by long-term administration of oral contraceptives in rats. Neuropharmacology. 2002;42:325-36 pubmed
    ..In rats this effect was associated with a plastic adaptation of GABA(A) receptor gene expression in the rat cerebral cortex. ..
  38. Uzunova V, Ceci M, Kohler C, Uzunov D, Wrynn A. Region-specific dysregulation of allopregnanolone brain content in the olfactory bulbectomized rat model of depression. Brain Res. 2003;976:1-8 pubmed
  39. Concas A, Follesa P, Barbaccia M, Purdy R, Biggio G. Physiological modulation of GABA(A) receptor plasticity by progesterone metabolites. Eur J Pharmacol. 1999;375:225-35 pubmed
    ..The results demonstrate that the changes in the plasticity of GABA(A) receptors that occur in rat brain during pregnancy and after delivery are related to the physiological changes in plasma and brain concentrations of neurosteroids. ..
  40. Ottander U, Poromaa I, Bjurulf E, Skytt A, Backstrom T, Olofsson J. Allopregnanolone and pregnanolone are produced by the human corpus luteum. Mol Cell Endocrinol. 2005;239:37-44 pubmed
    Using a dispersed human luteal cell culture model, progesterone, allopregnanolone and pregnanolone release following treatment by incremental doses of human chorionic gonadotrophin (hCG) were evaluated...
  41. Mellon S, Gong W, Griffin L. Niemann pick type C disease as a model for defects in neurosteroidogenesis. Endocr Res. 2004;30:727-35 pubmed
    ..These data suggest that neurosteroids play an important role in brain development and maturation and may be an effective therapy for NP-C and perhaps other lysosomal storage diseases. ..
  42. Griffin L, Gong W, Verot L, Mellon S. Niemann-Pick type C disease involves disrupted neurosteroidogenesis and responds to allopregnanolone. Nat Med. 2004;10:704-11 pubmed
    ..Earlier administration increases effectiveness of treatment. Decreased production of allopregnanolone apparently contributes to the pathology of NP-C; thus, neurosteroid treatment may be useful in ameliorating progression of the disease...
  43. Uzunova V, Wrynn A, Kinnunen A, Ceci M, Kohler C, Uzunov D. Chronic antidepressants reverse cerebrocortical allopregnanolone decline in the olfactory-bulbectomized rat. Eur J Pharmacol. 2004;486:31-4 pubmed
    ..We therefore propose that normalization of allopregnanolone cerebrocortical levels may contribute to the antidepressant-like profile of these drugs in the olfactory-bulbectomized rat model of depression. ..
  44. Goutman J, Calvo D. Studies on the mechanisms of action of picrotoxin, quercetin and pregnanolone at the GABA rho 1 receptor. Br J Pharmacol. 2004;141:717-27 pubmed
    ..of action of antagonists of the gamma-aminobutyric acid C (GABA(C)) receptor picrotoxin, quercetin and pregnanolone were studied. 2...
  45. Bernardi F, Pieri M, Stomati M, Luisi S, Palumbo M, Pluchino N, et al. Effect of different hormonal replacement therapies on circulating allopregnanolone and dehydroepiandrosterone levels in postmenopausal women. Gynecol Endocrinol. 2003;17:65-77 pubmed
    ..In conclusion, HRT strongly modifies circulating neurosteroid levels in postmenopausal women. ..
  46. Wang J, Johnston P, Ball B, Brinton R. The neurosteroid allopregnanolone promotes proliferation of rodent and human neural progenitor cells and regulates cell-cycle gene and protein expression. J Neurosci. 2005;25:4706-18 pubmed
    ..The therapeutic potential of allopregnanolone as a neurogenic molecule is discussed. ..
  47. Shannon E, Porcu P, Purdy R, Grant K. Characterization of the discriminative stimulus effects of the neuroactive steroid pregnanolone in DBA/2J and C57BL/6J inbred mice. J Pharmacol Exp Ther. 2005;314:675-85 pubmed
    ..Two neurosteroids, allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one) and pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one), possess anxiolytic and sedative properties and show substitution for ..
  48. Weill Engerer S, David J, Sazdovitch V, Liere P, Eychenne B, Pianos A, et al. Neurosteroid quantification in human brain regions: comparison between Alzheimer's and nondemented patients. J Clin Endocrinol Metab. 2002;87:5138-43 pubmed
    ..High levels of key proteins implicated in the formation of plaques and neurofibrillary tangles were correlated with decreased brain levels of PREGS and DHEAS, suggesting a possible neuroprotective role of these neurosteroids in AD. ..
  49. Liu Q, Chang Y, Schaffner A, Smith S, Barker J. Allopregnanolone activates GABA(A) receptor/Cl(-) channels in a multiphasic manner in embryonic rat hippocampal neurons. J Neurophysiol. 2002;88:1147-58 pubmed
    ..The results indicate that allopregnanolone interacts with GABA(A) receptor/Cl(-) channels expressed by embryonic hippocampal neurons in multiple ways, some of which are mediated by G proteins. ..
  50. Herbison A. Physiological roles for the neurosteroid allopregnanolone in the modulation of brain function during pregnancy and parturition. Prog Brain Res. 2001;133:39-47 pubmed
    ..The temporal correlation between these events and the observed cognitive, psychiatric and physiological changes associated with pregnancy and the peri-partum period in humans is striking and warrants close attention. ..
  51. Engel S, Purdy R, Grant K. Characterization of discriminative stimulus effects of the neuroactive steroid pregnanolone. J Pharmacol Exp Ther. 2001;297:489-95 pubmed
    Reduced pregnane neurosteroids such as allopregnanolone and pregnanolone are potent neuromodulators able to affect a number of membrane receptors, including gamma-aminobutyric acid (GABA)(A), N-methyl-D-aspartate (NMDA), 5-..
  52. Bitran D, Dugan M, Renda P, Ellis R, Foley M. Anxiolytic effects of the neuroactive steroid pregnanolone (3 alpha-OH-5 beta-pregnan-20-one) after microinjection in the dorsal hippocampus and lateral septum. Brain Res. 1999;850:217-24 pubmed
    The anxiolytic effects of the neuroactive steroid, 3 alpha-OH-5 beta-pregnan-20-one (pregnanolone), were determined after injection into the dorsal hippocampus or lateral septum in adult male rats...
  53. Nicol M, Hirst J, Walker D. Effects of pregnanolone on behavioural parameters and the responses to GABA(A) receptor antagonists in the late gestation fetal sheep. Neuropharmacology. 1999;38:49-63 pubmed
    ..In an initial study, the effect of 5beta-pregnan-3alpha-ol-20-one (pregnanolone) given as a bolus (2.5 and 5...