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]]
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[[fr:Prégnénolone]]
[[he:פרגננולון]]
[[ja:プレグネノロン]]