pregnenolone

Summary

Summary: A 21-carbon steroid, derived from CHOLESTEROL and found in steroid hormone-producing tissues. Pregnenolone is the precursor to GONADAL STEROID HORMONES and the adrenal CORTICOSTEROIDS.

Top Publications

  1. Schumacher M, Liere P, Akwa Y, Rajkowski K, Griffiths W, Bodin K, et al. Pregnenolone sulfate in the brain: a controversial neurosteroid. Neurochem Int. 2008;52:522-40 pubmed
    b>Pregnenolone sulfate (PREGS) has been shown, either at high nanomolar or at micromolar concentrations, to increase neuronal activity by inhibiting GABAergic and by stimulating glutamatergic neurotransmission...
  2. Kostakis E, Jang M, Russek S, Gibbs T, Farb D. A steroid modulatory domain in NR2A collaborates with NR1 exon-5 to control NMDAR modulation by pregnenolone sulfate and protons. J Neurochem. 2011;119:486-96 pubmed publisher
    ..The neuroactive steroid pregnenolone sulfate (PS) acts as a cognitive enhancer in impaired animals, augments LTP in hippocampal slices by enhancing ..
  3. Karri S, Dertien J, Stocco D, Syapin P. Steroidogenic acute regulatory protein expression and pregnenolone synthesis in rat astrocyte cultures. J Neuroendocrinol. 2007;19:860-9 pubmed
    ..P450-side chain cleavage enzyme was demonstrated with a specific antibody, indicating the potential for pregnenolone production in these cells...
  4. Hill M, Havlikova H, Vrbikova J, Kancheva R, Kancheva L, Pouzar V, et al. The identification and simultaneous quantification of 7-hydroxylated metabolites of pregnenolone, dehydroepiandrosterone, 3beta,17beta-androstenediol, and testosterone in human serum using gas chromatography-mass spectrometry. J Steroid Biochem Mol Biol. 2005;96:187-200 pubmed
    ..A gas chromatography-mass spectrometry (GC-MS) method for the determination of 7-hydroxy-metabolites of pregnenolone, DHEA, AD, and testosterone including the parent steroids was applied to serum samples from 12 adult men (27-66 ..
  5. Lee K, Fuda H, Lee Y, Negishi M, Strott C, Pedersen L. Crystal structure of human cholesterol sulfotransferase (SULT2B1b) in the presence of pregnenolone and 3'-phosphoadenosine 5'-phosphate. Rationale for specificity differences between prototypical SULT2A1 and the SULT2BG1 isoforms. J Biol Chem. 2003;278:44593-9 pubmed
    ..SULT2B1b has a predilection for cholesterol but is also capable of sulfonating pregnenolone, whereas SULT2B1a preferentially sulfonates pregnenolone and only minimally sulfonates cholesterol...
  6. Weng J, Liang M, Chen C, Tong S, Huang T, Lee S, et al. Pregnenolone activates CLIP-170 to promote microtubule growth and cell migration. Nat Chem Biol. 2013;9:636-42 pubmed publisher
    b>Pregnenolone (P5) is a neurosteroid that improves memory and neurological recovery. It is also required for zebrafish embryonic development. However, its mode of action is unclear...
  7. Strushkevich N, MacKenzie F, Cherkesova T, Grabovec I, Usanov S, Park H. Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system. Proc Natl Acad Sci U S A. 2011;108:10139-43 pubmed publisher
    In humans, the precursor to all steroid hormones, pregnenolone, is synthesized from cholesterol by an enzyme complex comprising adrenodoxin reductase (AdR), adrenodoxin (Adx), and a cytochrome P450 (P450scc or CYP11A1)...
  8. Baker B, Epand R, Epand R, Miller W. Cholesterol binding does not predict activity of the steroidogenic acute regulatory protein, StAR. J Biol Chem. 2007;282:10223-32 pubmed
    ..and gonadal steroidogenesis by increasing the influx of cholesterol into mitochondria, where it is converted to pregnenolone to initiate steroidogenesis...
  9. 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
    ..When fetal brains were collected 1 h after a 10 min UCO, the relative increases of AP and pregnenolone content in the parietal cortex were similar to the increase observed in the extracellular (dialysate) fluid...

More Information

Publications62

  1. Porcu P, Rogers L, Morrow A, Grant K. Plasma pregnenolone levels in cynomolgus monkeys following pharmacological challenges of the hypothalamic-pituitary-adrenal axis. Pharmacol Biochem Behav. 2006;84:618-27 pubmed
    b>Pregnenolone (PREG) is an endogenous neuroactive steroid that is increased in rodent brain and plasma after hypothalamic-pituitary-adrenal (HPA) activation by acute stress or ethanol administration...
  2. 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
    ..The 3beta-PI and sulfates of PI and pregnenolone exert the opposite effect...
  3. Lee K, Cho J, Choi I, Park H, Lee M, Choi B, et al. Pregnenolone sulfate enhances spontaneous glutamate release by inducing presynaptic Ca2+-induced Ca2+ release. Neuroscience. 2010;171:106-16 pubmed publisher
    b>Pregnenolone sulfate (PS) acts as an excitatory neuromodulator and has a variety of neuropharmacological actions, such as memory enhancement and convulsant effects...
  4. Majeed Y, Agarwal A, Naylor J, Seymour V, Jiang S, Muraki K, et al. Cis-isomerism and other chemical requirements of steroidal agonists and partial agonists acting at TRPM3 channels. Br J Pharmacol. 2010;161:430-41 pubmed publisher
    ..melastatin-3 (TRPM3) channel forms calcium-permeable, non-selective, cationic channels that are stimulated by pregnenolone sulphate (PregS)...
  5. Majeed Y, Tumova S, Green B, Seymour V, Woods D, Agarwal A, et al. Pregnenolone sulphate-independent inhibition of TRPM3 channels by progesterone. Cell Calcium. 2012;51:1-11 pubmed publisher
    ..channel that is stimulated by high concentrations of nifedipine or by physiological steroids that include pregnenolone sulphate. Here we sought to identify steroids that inhibit TRPM3...
  6. Yan C, Hou Y. Effects of morphine dependence and withdrawal on levels of neurosteroids in rat brain. Acta Pharmacol Sin. 2004;25:1285-91 pubmed
    ..To investigate the effects of morphine dependence and withdrawal on the concentrations of neurosteroids in rat brain...
  7. Guryev O, Carvalho R, Usanov S, Gilep A, Estabrook R. A pathway for the metabolism of vitamin D3: unique hydroxylated metabolites formed during catalysis with cytochrome P450scc (CYP11A1). Proc Natl Acad Sci U S A. 2003;100:14754-9 pubmed
    ..Although the physiological importance of these hydroxylated metabolites of D3 and their in vivo formation and mode of action remain to be determined, the rate with which they are formed by CYP11A1 in vitro suggests an important role. ..
  8. Kostakis E, Smith C, Jang M, Martin S, Richards K, Russek S, et al. The neuroactive steroid pregnenolone sulfate stimulates trafficking of functional N-methyl D-aspartate receptors to the cell surface via a noncanonical, G protein, and Ca2+-dependent mechanism. Mol Pharmacol. 2013;84:261-74 pubmed publisher
    ..of schizophrenia, and clinical studies have revealed reduced negative symptoms of schizophrenia with a dose of pregnenolone that elevates serum levels of the neuroactive steroid pregnenolone sulfate (PregS)...
  9. Ahboucha S, Pomier Layrargues G, Mamer O, Butterworth R. Increased levels of pregnenolone and its neuroactive metabolite allopregnanolone in autopsied brain tissue from cirrhotic patients who died in hepatic coma. Neurochem Int. 2006;49:372-8 pubmed
    ..In order to address this issue, gas chromatography/mass spectrometry was used to measure the neurosteroids pregnenolone, allopregnanolone, and tetrahydrodeoxycorticosterone (THDOC) in postmortem brain tissue from controls, ..
  10. Zamudio Bulcock P, Valenzuela C. Pregnenolone sulfate increases glutamate release at neonatal climbing fiber-to-Purkinje cell synapses. Neuroscience. 2011;175:24-36 pubmed publisher
    ..Developing hippocampal pyramidal neurons retrogradely release a pregnenolone sulfate (PregS)-like neurosteroid that may contribute to glutamatergic synapse stabilization...
  11. Mameli M, Carta M, Partridge L, Valenzuela C. Neurosteroid-induced plasticity of immature synapses via retrograde modulation of presynaptic NMDA receptors. J Neurosci. 2005;25:2285-94 pubmed
    ..We report here that the excitatory neurosteroid pregnenolone sulfate induces a long-lasting strengthening of AMPA receptor-mediated synaptic transmission in rat hippocampal ..
  12. Wagner T, Loch S, Lambert S, Straub I, Mannebach S, Mathar I, et al. Transient receptor potential M3 channels are ionotropic steroid receptors in pancreatic beta cells. Nat Cell Biol. 2008;10:1421-30 pubmed publisher
    ..show here that TRPM3, a divalent-permeable cation channel, is rapidly and reversibly activated by extracellular pregnenolone sulphate, a neuroactive steroid...
  13. Sun X, Cheng F, Meng B, Yang B, Song W, Yuan H. Pregnenolone sulfate decreases intraocular pressure and changes expression of sigma receptor in a model of chronic ocular hypertension. Mol Biol Rep. 2012;39:6607-14 pubmed publisher
    ..This study describes the effect of the sigma receptor 1 agonist pregnenolone sulfate on intraocular pressure (IOP) and sigma receptor 1 expression in rat retinas after chronic ocular ..
  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
    ..We therefore investigated prefrontal cortex (PFC) NS levels in AD. Neurosteroid levels (allopregnanolone, pregnenolone, dehydroepiandrosterone [DHEA]) were determined in postmortem PFC in 14 male subjects with AD and 15 ..
  15. Loomis W, Behrens M, Williams M, Anjard C. Pregnenolone sulfate and cortisol induce secretion of acyl-CoA-binding protein and its conversion into endozepines from astrocytes. J Biol Chem. 2010;285:21359-65 pubmed publisher
    ..we now show that astrocytes release the endozepine peptides within 10 min of exposure to the steroids cortisol, pregnenolone, pregnenolone sulfate, or progesterone...
  16. Ritsner M, Maayan R, Gibel A, Weizman A. Differences in blood pregnenolone and dehydroepiandrosterone levels between schizophrenia patients and healthy subjects. Eur Neuropsychopharmacol. 2007;17:358-65 pubmed
    ..DHEA) levels in schizophrenia led us to compare the serum concentration of its precursor, pregnenolone (PREG), between medicated schizophrenia patients and healthy subjects...
  17. Chen S, Liu B, Chen C, Wu F. Intradermal pregnenolone sulfate attenuates capsaicin-induced nociception in rats. Biochem Biophys Res Commun. 2006;349:626-33 pubmed
    We have previously shown that the neurosteroid pregnenolone sulfate (PS) inhibits the capsaicin receptor-mediated current in rat dorsal root ganglion neurons...
  18. Marx C, Shampine L, Duncan G, VanDoren M, Grobin A, Massing M, et al. Clozapine markedly elevates pregnenolone in rat hippocampus, cerebral cortex, and serum: candidate mechanism for superior efficacy?. Pharmacol Biochem Behav. 2006;84:598-608 pubmed
    ..b>Pregnenolone administration improves learning and memory in rodent models, and decreases in this NS have been associated ..
  19. Horishita T, Minami K, Uezono Y, Shiraishi M, Ogata J, Okamoto T, et al. The effects of the neurosteroids: pregnenolone, progesterone and dehydroepiandrosterone on muscarinic receptor-induced responses in Xenopus oocytes expressing M1 and M3 receptors. Naunyn Schmiedebergs Arch Pharmacol. 2005;371:221-8 pubmed
    The neurosteroids pregnenolone, progesterone, and dehydroepiandrosterone (DHEA) occur naturally in the nervous system...
  20. Slominski A, Zjawiony J, Wortsman J, Semak I, Stewart J, Pisarchik A, et al. A novel pathway for sequential transformation of 7-dehydrocholesterol and expression of the P450scc system in mammalian skin. Eur J Biochem. 2004;271:4178-88 pubmed
    ..cytochrome P450 side-chain cleavage (P450scc) system required for the intracellular catalytic production of pregnenolone, i.e. the genes and proteins for P450scc enzyme, adrenodoxin, adrenodoxin reductase and MLN64...
  21. Tuckey R. Progesterone synthesis by the human placenta. Placenta. 2005;26:273-81 pubmed
    ..The rate-determining step of placental progesterone synthesis is the conversion of cholesterol to pregnenolone by cytochrome P450scc (CYP11A1) in placental mitochondria in a reaction requiring electrons delivered via ..
  22. Shirakawa H, Katsuki H, Kume T, Kaneko S, Akaike A. Pregnenolone sulphate attenuates AMPA cytotoxicity on rat cortical neurons. Eur J Neurosci. 2005;21:2329-35 pubmed
    ..e. neuronal cell death triggered by over-activation of glutamate receptors. It has been reported that pregnenolone sulphate (PS) and pregnenolone hemisuccinate (PHS) augment N-methyl-D-aspartate (NMDA) neurotoxicity in rat ..
  23. Sliwinski A, Monnet F, Schumacher M, Morin Surun M. Pregnenolone sulfate enhances long-term potentiation in CA1 in rat hippocampus slices through the modulation of N-methyl-D-aspartate receptors. J Neurosci Res. 2004;78:691-701 pubmed
    Among the different steroids found in the brain, pregnenolone sulfate (3beta-hydroxy-5-pregnen-20-one-3-sulfate; PREGS) is known to enhance hippocampal-associated memory...
  24. Williamson J, Mtchedlishvili Z, Kapur J. Characterization of the convulsant action of pregnenolone sulfate. Neuropharmacology. 2004;46:856-64 pubmed
    b>Pregnenolone sulfate (PS) is an endogenous neurosteroid synthesized by glial cells, which acts as a potent convulsant when injected intracerebroventricularly and intraperitoneally...
  25. Marx C, Keefe R, Buchanan R, Hamer R, Kilts J, Bradford D, et al. Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia. Neuropsychopharmacology. 2009;34:1885-903 pubmed publisher
    The neurosteroid pregnenolone and its sulfated derivative enhance learning and memory in rodents...
  26. Chen L, Sokabe M. Presynaptic modulation of synaptic transmission by pregnenolone sulfate as studied by optical recordings. J Neurophysiol. 2005;94:4131-44 pubmed
    The effects of pregnenolone sulfate (PREGS), a putative neurosteroid, on the transmission of perforant path-granule cell synapses were investigated with an optical recording technique in rat hippocampal slices stained with voltage-..
  27. Wong P, Chang C, Marx C, Caron M, Wetsel W, Zhang X. Pregnenolone rescues schizophrenia-like behavior in dopamine transporter knockout mice. PLoS ONE. 2012;7:e51455 pubmed publisher
    b>Pregnenolone belongs to a class of endogenous neurosteroids in the central nervous system (CNS), which has been suggested to enhance cognitive functions through GABA(A) receptor signaling by its metabolites...
  28. O Dell L, Alomary A, Vallée M, Koob G, Fitzgerald R, Purdy R. Ethanol-induced increases in neuroactive steroids in the rat brain and plasma are absent in adrenalectomized and gonadectomized rats. Eur J Pharmacol. 2004;484:241-7 pubmed
    ..p.). Concentrations of pregnenolone, allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), and allotetrahydrodeoxycorticosterone (3alpha,21-..
  29. Kohjitani A, Fuda H, Hanyu O, Strott C. Regulation of SULT2B1a (pregnenolone sulfotransferase) expression in rat C6 glioma cells: relevance of AMPA receptor-mediated NO signaling. Neurosci Lett. 2008;430:75-80 pubmed
    The neurosteroid pregnenolone sulfate (PREGS), which is synthesized in glial cells, plays a significant role in learning and memory performance...
  30. Mòdol L, Darbra S, Pallares M. Neurosteroids infusion into the CA1 hippocampal region on exploration, anxiety-like behaviour and aversive learning. Behav Brain Res. 2011;222:223-9 pubmed publisher
    ..as pregnanolone or allopregnanolone (Allop), or GABAA negative modulators and NMDA positive modulators as pregnenolone (PREG) or dehydroepiandrosterone (DHEA) and their sulphate esters (PREGS and DHEAS)...
  31. Darbra S, Pallares M. Interaction between early postnatal neurosteroid manipulations and adult infusion of neurosteroids into CA1 hippocampal region on the open field behaviour. Behav Brain Res. 2011;216:705-11 pubmed publisher
    ..present work is to investigate whether the effects of adult CA1 intrahippocampal administrations of AlloP and pregnenolone sulphate (PregS), GABAA positive and negative modulators, respectively, on behavioural novelty responses ..
  32. Chen S, Wu F. Mechanism underlying inhibition of the capsaicin receptor-mediated current by pregnenolone sulfate in rat dorsal root ganglion neurons. Brain Res. 2004;1027:196-200 pubmed
    The effect of pregnenolone sulfate (PS) on the capsaicin receptor-mediated current was studied in acutely dissociated rat dorsal root ganglion neurons using the whole-cell voltage-clamp technique...
  33. Sedlacek M, Korinek M, Petrovic M, Cais O, Adamusová E, Chodounska H, et al. Neurosteroid modulation of ionotropic glutamate receptors and excitatory synaptic transmission. Physiol Res. 2008;57 Suppl 3:S49-57 pubmed
    ..exogenously applied glutamate are potentiated or inhibited (depending on the receptor subunit composition) by pregnenolone sulphate (PS) and inhibited by pregnanolone sulphate (3alpha5betaS)...
  34. Hill M, Popov P, Havlikova H, Kancheva L, Vrbikova J, Kancheva R, et al. Altered profiles of serum neuroactive steroids in premenopausal women treated for alcohol addiction. Steroids. 2005;70:515-24 pubmed
    ..Some progesterone metabolites, including three pregnanolone isomers (PI), abate, while pregnenolone sulfate (PregS) and dehydroepiandrosterone sulfate (DHEAS) increase, alcohol tolerance...
  35. Marx C, Shampine L, Khisti R, Trost W, Bradford D, Grobin A, et al. Olanzapine and fluoxetine administration and coadministration increase rat hippocampal pregnenolone, allopregnanolone and peripheral deoxycorticosterone: implications for therapeutic actions. Pharmacol Biochem Behav. 2006;84:609-17 pubmed
    ..It is unknown if these agents also alter pregnenolone or deoxycorticosterone...
  36. Chávez Delgado M, Gomez Pinedo U, Feria Velasco A, Huerta Viera M, Castañeda S, Toral F, et al. Ultrastructural analysis of guided nerve regeneration using progesterone- and pregnenolone-loaded chitosan prostheses. J Biomed Mater Res B Appl Biomater. 2005;74:589-600 pubmed
    ..In this study, chitosan prostheses containing neurosteroids (progesterone and pregnenolone) were used for bridging a 10-mm gap in the rabbit facial nerve...
  37. Dhir A, Kulkarni S. Involvement of sigma (sigma1) receptors in modulating the anti-depressant effect of neurosteroids (dehydroepiandrosterone or pregnenolone) in mouse tail-suspension test. J Psychopharmacol. 2008;22:691-6 pubmed publisher
    The present study investigated the effects of neurosteroids dehydroepiandrosterone sulfate (DHEAS) or pregnenolone sulfate (PS) on the tail-suspension test (TST) of depression in mice, and also the possible involvement of sigma (sigma) ..
  38. Ducharme N, Banks W, Morley J, Robinson S, Niehoff M, Mattern C, et al. Brain distribution and behavioral effects of progesterone and pregnenolone after intranasal or intravenous administration. Eur J Pharmacol. 2010;641:128-34 pubmed publisher
    ..We compared the uptake by 11 brain regions and appearance in blood of tritium-labeled pregnenolone and progesterone after intranasal and intravenous (IV) injection...
  39. Lombardi I, Luisi S, Quirici B, Monteleone P, Bernardi F, Liut M, et al. Adrenal response to adrenocorticotropic hormone stimulation in patients with premenstrual syndrome. Gynecol Endocrinol. 2004;18:79-87 pubmed
    ..dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), androstenedione, total and free testosterone, cortisol, pregnenolone and allopregnanolone levels in 20 patients suffering from PMS and to compare them with those found in 20 ..
  40. Hauet T, Yao Z, Bose H, Wall C, Han Z, Li W, et al. Peripheral-type benzodiazepine receptor-mediated action of steroidogenic acute regulatory protein on cholesterol entry into leydig cell mitochondria. Mol Endocrinol. 2005;19:540-54 pubmed
    ..Tom20 (translocase of outer membrane) and StAR (Tom/StAR) to mitochondria isolated from control cells increased pregnenolone formation...
  41. Hojo Y, Hattori T, Enami T, Furukawa A, Suzuki K, Ishii H, et al. Adult male rat hippocampus synthesizes estradiol from pregnenolone by cytochromes P45017alpha and P450 aromatase localized in neurons. Proc Natl Acad Sci U S A. 2004;101:865-70 pubmed
    ..Analysis of radioactive metabolites demonstrated the conversion from [(3)H]pregnenolone to [(3)H]estradiol through dehydroepiandrosterone and testosterone...
  42. Caldeira J, Wu Y, Mameli M, Purdy R, Li P, Akwa Y, et al. Fetal alcohol exposure alters neurosteroid levels in the developing rat brain. J Neurochem. 2004;90:1530-9 pubmed
    ..A prenatal ethanol exposure-induced increase in pregnenolone sulfate levels, but not dehydroepiandrosterone sulfate levels, was evident at the earliest time point studied (..
  43. Majeed Y, Amer M, Agarwal A, McKeown L, Porter K, O Regan D, et al. Stereo-selective inhibition of transient receptor potential TRPC5 cation channels by neuroactive steroids. Br J Pharmacol. 2011;162:1509-20 pubmed publisher
    ..Native TRPC channel activity was recorded from vascular smooth muscle cells. Extracellular application of pregnenolone sulphate, pregnanolone sulphate, pregnanolone, progesterone or dihydrotestosterone inhibited TRPC5 activity ..
  44. Kushnir M, Rockwood A, Roberts W, Pattison E, Owen W, Bunker A, et al. Development and performance evaluation of a tandem mass spectrometry assay for 4 adrenal steroids. Clin Chem. 2006;52:1559-67 pubmed
    ..Analysis of 11-deoxycortisol (11DC), 17-hydroxyprogesterone (17OHP), 17-hydroxypregnenolone (17OHPr), and pregnenolone (Pr) in blood allows detection of these enzyme defects...
  45. Ritsner M, Gibel A, Shleifer T, Boguslavsky I, Zayed A, Maayan R, et al. Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial. J Clin Psychiatry. 2010;71:1351-62 pubmed publisher
    b>Pregnenolone (PREG) and dehydroepiandrosterone (DHEA) are reported to have a modulatory effect on neuronal excitability, synaptic plasticity, and response to stress; they are associated with mood regulation and cognitive performance...
  46. Costa B, Pini S, Gabelloni P, Da Pozzo E, Abelli M, Lari L, et al. The spontaneous Ala147Thr amino acid substitution within the translocator protein influences pregnenolone production in lymphomonocytes of healthy individuals. Endocrinology. 2009;150:5438-45 pubmed publisher
    The de novo production of steroids and neurosteroids begins in mitochondria by the conversion of cholesterol to pregnenolone through cytochrome P450 side-chain cleavage (CYP11A1) enzymatic activity...
  47. Marx C, Bradford D, Hamer R, Naylor J, Allen T, Lieberman J, et al. Pregnenolone as a novel therapeutic candidate in schizophrenia: emerging preclinical and clinical evidence. Neuroscience. 2011;191:78-90 pubmed publisher
    Emerging preclinical and clinical evidence suggests that pregnenolone may be a promising novel therapeutic candidate in schizophrenia...
  48. Whittaker M, Gibbs T, Farb D. Pregnenolone sulfate induces NMDA receptor dependent release of dopamine from synaptic terminals in the striatum. J Neurochem. 2008;107:510-21 pubmed publisher
    ..b>Pregnenolone sulfate (PS) modulates both ionotropic glutamate and GABA(A) receptor mediated synaptic transmission...
  49. Liu T, Wimalasena J, Bowen R, Atwood C. Luteinizing hormone receptor mediates neuronal pregnenolone production via up-regulation of steroidogenic acute regulatory protein expression. J Neurochem. 2007;100:1329-39 pubmed
    ..hippocampal neurons and human M17 neuroblastoma cells with LH (100 mIU/mL) resulted in a twofold increase in pregnenolone secretion in both cell types, suggesting an increase in P450scc-mediated cleavage of cholesterol to ..
  50. Cauet G, Degryse E, Ledoux C, Spagnoli R, Achstetter T. Pregnenolone esterification in Saccharomyces cerevisiae. A potential detoxification mechanism. Eur J Biochem. 1999;261:317-24 pubmed
    While studying the effect of steroids on the growth of the yeast Saccharomyces cerevisiae, we found that pregnenolone was converted into the acetate ester...
  51. Naylor J, Li J, Milligan C, Zeng F, Sukumar P, Hou B, et al. Pregnenolone sulphate- and cholesterol-regulated TRPM3 channels coupled to vascular smooth muscle secretion and contraction. Circ Res. 2010;106:1507-15 pubmed publisher
    Transient receptor potential melastatin (TRPM)3 is a calcium-permeable ion channel activated by the neurosteroid pregnenolone sulfate and positively coupled to insulin secretion in beta cells...
  52. Burel D, Li J, Do Rego J, Wang A, Luu The V, Pelletier G, et al. Gonadotropin-releasing hormone stimulates the biosynthesis of pregnenolone sulfate and dehydroepiandrosterone sulfate in the hypothalamus. Endocrinology. 2013;154:2114-28 pubmed publisher
    The sulfated neurosteroids pregnenolone sulfate (?(5)PS) and dehydroepiandrosterone sulfate (DHEAS) are known to play a role in the control of reproductive behavior...
  53. Hsu H, Liang M, Chen C, Chung B. Pregnenolone stabilizes microtubules and promotes zebrafish embryonic cell movement. Nature. 2006;439:480-3 pubmed
    ..Here we report that pregnenolone, which is produced from cholesterol by the steroidogenic enzyme Cyp11a1 (cholesterol side-chain cleavage enzyme,..