Pregnenolone 2182714 222833504 2008-07-01T09:58:10Z 128.250.6.247 {{drugbox | IUPAC_name = 3β-hydroxypregn-5-en-20-one | image = Pregnenolone.png | CAS_number = 145-13-1 | ATC_prefix = | ATC_suffix = | ATC_supplemental = | PubChem = 8955 | DrugBank = EXPT02608 | C=21 | H=32 | O=2 | molecular_weight = 316.483 g/mol | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion = | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_US = <!-- A / B / C / D / X --> | pregnancy_category = | legal_AU = <!-- Unscheduled / S2 / S4 / S8 --> | legal_UK = <!-- GSL / P / POM / CD --> | legal_US = <!-- OTC / Rx-only --> | legal_status = | routes_of_administration = }} '''Pregnenolone''' is a [[steroid]] hormone involved in the [[steroidogenesis]] of [[progesterone]], [[mineralocorticoids]], [[glucocorticoids]], [[androgen]]s, and [[estrogen]]s. As such it is a [[prohormone]]. Pregnenolone is a [[GABAB receptor|GABA<sub>B</sub>]] antagonist and increases neurogenesis in the hippocampus.<ref name=Mayo2005>{{cite journal | pmid = 15585350 | pmc = 15585350 | title = Pregnenolone Sulfate Enhances Neurogenesis and Psa-Ncam in Young and Aged Hippocampus | year = 2005 | journal = Neurobiology of Aging | volume = 26 | issue = 1 | pages = 103–14 | doi = 10.1016/j.neurobiolaging.2004.03.013 | month = Jan | author = Mayo, W; Lemaire, V; Malaterre, J; Rodriguez, Jj; Cayre, M; Stewart, Mg; Kharouby, M; Rougon, G; Le, Moal, M; Piazza, Pv; Abrous, Dn }}</ref> ==Chemistry== Like other [[steroid]]s, pregnenolone consists of four interconnected [[cyclic hydrocarbon]]s. It contains [[ketone]] and [[hydroxyl]] functional groups, two [[methyl]] branches, and a double bond at C5, in the B cyclic hydrocarbon ring. Like all steroid hormones, it is [[hydrophobic]]. Its esterified version, pregnenolone sulfate, is water-soluble. ==Synthesis== [[Image:DHEA1.svg|thumb|350px|''Production of Pregnenolone from Cholesteol and further metabolism'']] [[Image:Reaction-Pregnenolone-Progesterone2.png|thumb|350px|Reaction: Pregnenolone-[[Progesterone]]]] Pregnenolone is synthesized from [[cholesterol]]. This conversion involves hydroxylation at the [[side-chain]] at C20 and C22 positions, with cleavage of the side-chain. The [[enzyme]] performing this task is [[P450 scc|cytochrome P450scc]], located in the [[mitochondria]], and controlled by pituitary tropic hormones, such as [[ACTH]], [[FSH]], [[LH]]. ==Prohormone== Pregnenolone undergoes further steroid metabolism in one of three ways. * Pregnenolone can be converted to [[progesterone]]. The critical enzyme step is two-fold using a [[3-beta-hydroxysteroid dehydrogenase]] and a [[delta 4-5 isomerase]]. The latter transfers the [[double bond]] from C5 to C4 on the A ring. Progesterone is the entry into the [[delta-4-pathway]], resulting in production of 17-hydroxy progesterone and [[androstenedione]], precursor to [[testosterone]] and [[estrone]]. [[Aldosterone]] and [[corticosteroid]]s are also derived from progesterone or its derivatives. * Pregnenolone can be converted to [[17-hydroxy-pregnenolone]] by the enzyme 17α-hydroxylase ([[CYP17A1]]). Using this pathway, termed [[delta-5 pathway]], the next step is conversion to [[dehydroepiandrosterone]] (DHEA) using a [[desmolase]]. DHEA is the precursor of androstenedione. * Pregnenolone can be converted to androsta-5,16-dien-3 beta-ol by 16-ene synthetase. ==Neurosteroid== Pregnenolone and its sulfate, like [[dehydroepiandrosterone]] and its sulfate and progesterone, belong to the group of [[neuroactive steroid|neurosteroid]]s that are found in high concentrations in certain areas in the brain, and are synthesized there. Neurosteroids affect synaptic functioning, are [[neuroprotective]], and enhance [[myelin]]ization. Pregnenolone and its sulfate ester are under investigation for their potential to improve cognitive and [[memory]] functioning.<ref>{{cite journal | author = Vallée M, Mayo W, Le Moal M | title = Role of pregnenolone, dehydroepiandrosterone and their sulfate esters on learning and memory in cognitive aging. | journal = Brain Res Brain Res Rev | volume = 37 | issue = 1-3 | pages = 301–12 | year = 2001 | pmid = 11744095 | doi = 10.1016/S0165-0173(01)00135-7}}</ref> ==Additional images== <gallery> Image:Steroidogenesis.gif|[[Steroidogenesis]] Image:Cholesterol.svg|[[Cholesterol]] Image:Progesterone-2D-skeletal.png|[[Progesterone]] </gallery> ==References== {{Reflist}} {{Steroids}} [[Category:Steroid hormones]] [[Category:Neurosteroids]] [[de:Pregnenolon]] [[fr:Prégnénolone]] [[he:פרגננולון]] [[ja:プレグネノロン]]