Pregnenolone

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'''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
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| pmid = 15585350
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| pmc = 15585350
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| title = Pregnenolone Sulfate Enhances Neurogenesis and Psa-Ncam in Young and Aged Hippocampus
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| year = 2005
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| journal = Neurobiology of Aging
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| volume = 26
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| issue = 1
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| pages = 103–14
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| doi = 10.1016/j.neurobiolaging.2004.03.013
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| month = Jan
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| 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>
 +
Pubchem(8955)
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<table align='right' border=1>
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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.
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<jmol><jmolApplet>
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<script>spin on;color atoms amino;</script>
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<uploadedFileContents>NPH207.SDF</uploadedFileContents>
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</jmol>
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</td></tr></table>
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==Description==
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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.
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==General Properties==
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<b>*Molecular Weight</b>
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'''Drug Type''':  Small Molecule; Experimental
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316.48
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'''KEGG Pathway'''(C01953,D00143)
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*C21-Steroid hormone metabolism
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{| border="1;width:100%; height:200px;style=text-align:center"
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|+'''Physiochemical properties of Estriol:'''
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|-
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! style="background:brown; color:white" |Physical Property
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! style="background:brown; color:white" |Value
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! style="background:brown; color:white" |Units
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! style="background:brown; color:white" |Temp (deg C)
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! style="background:brown; color:white" |Source
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|-
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|Melting Point
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|192
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|deg C
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|  
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|EXP
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|-
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|log P (octanol-water)
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|4.22
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|(none)
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|
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|EXP
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|-
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|Water Solubility
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|7.06
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|mg/L
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|37
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|EXP
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|-
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|Vapor Pressure
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|1.03E-08
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|mm Hg
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|25
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|EST
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|-
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|Henry's Law Constant
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|1.17E-08
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|atm-m3/mole
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|25
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|EST
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|-
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|Atmospheric OH Rate Constant
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|1.20E-10
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|cm3/molecule-sec
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|25
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|EST
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|-
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|}
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{| border="1;width:100%; height:200px;style=text-align:center"
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|+'''Toxicity:'''
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|-
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! style="background:brown; color:white" |Organism
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! style="background:brown; color:white" |Test Type 
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! style="background:brown; color:white" |Route 
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! style="background:brown; color:white" |Reported Dose (Normalized Dose)
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! style="background:brown; color:white" |Effect
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! style="background:brown; color:white" |Source
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|-
 +
|mouse
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|LD
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|intraperitoneal
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|> 200mg/kg (200mg/kg)
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|  
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|Journal of Medicinal Chemistry. Vol. 11, Pg. 117, 1968.
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|-
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|}
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<b>*Molecular Formula</b>
 
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C<sub>2</sub><sub>1</sub>H<sub>3</sub><sub>2</sub>O<sub>2</sub>
 
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<b>*IUPAC NAME</b>
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==Chemistry==
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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.
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1-[(3S,8S,9S,10R,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone
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==Synthesis==
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[[Image:DHEA1.svg|thumb|350px|''Production of Pregnenolone from Cholesteol and further metabolism'']]
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[[Image:Reaction-Pregnenolone-Progesterone2.png|thumb|350px|Reaction: Pregnenolone-[[Progesterone]]]]
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<b>*Canonical Smiles</b>
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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]].
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CC(=O)C1CCC2C1(CCC3C2CC=C4C3(CCC(C4)O)C)C
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==Prohormone==
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Pregnenolone undergoes further steroid metabolism in one of three ways.
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<b>*Isomeric Smiles</b>
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* 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.
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CC(=O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CC=C4[C@@]3(CC[C@@H](C4)O)C)C
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* 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.
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* Pregnenolone can be converted to androsta-5,16-dien-3 beta-ol by 16-ene synthetase.
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==PhysioChemical Properties==
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==Neurosteroid==
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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>
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<b>*Melting Point</b>
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==Additional images==
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<gallery>
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Image:Steroidogenesis.svg|[[Steroidogenesis]]
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Image:Cholesterol.svg|[[Cholesterol]]
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Image:Progesterone-2D-skeletal.png|[[Progesterone]]
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</gallery>
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192(EXP)
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==References==
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{{Reflist}}
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<b>*LogP</b>
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{{Steroids}}
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[[Category:Steroid hormones]]
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4.22(EXP)
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[[Category:Neurosteroids]]
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<b>*Water Solubility</b>
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7.06(EXP) at 37C
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==External Links==
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*[http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=8955]Pubchem
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*[http://www.genome.jp/dbget-bin/www_bget?compound+C01953]KEGG Compound
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*[http://www.genome.jp/dbget-bin/www_bget?drug+D00143]KEGG Drug
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*[http://www.drugbank.ca/drugs/DB02789]Drugbank
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[[Categories:Hormones]]
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Revision as of 07:12, 13 February 2009

Pregnenolone is a steroid hormone involved in the steroidogenesis of progesterone, mineralocorticoids, glucocorticoids, androgens, and estrogens. As such it is a prohormone. Pregnenolone is a GABAB antagonist and increases neurogenesis in the hippocampus.<ref name=Mayo2005>Mayo, W; Lemaire, V; Malaterre, J; Rodriguez, Jj; Cayre, M; Stewart, Mg; Kharouby, M; Rougon, G; Le, Moal, M; Piazza, Pv; Abrous, Dn (Jan 2005). "Pregnenolone Sulfate Enhances Neurogenesis and Psa-Ncam in Young and Aged Hippocampus". Neurobiology of Aging 26 (1): 103–14. doi:10.1016/j.neurobiolaging.2004.03.013. PMID 15585350. </ref>

Pubchem(8955)

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.

Drug Type: Small Molecule; Experimental

KEGG Pathway(C01953,D00143)

  • C21-Steroid hormone metabolism
Physiochemical properties of Estriol:
Physical Property Value Units Temp (deg C) Source
Melting Point 192 deg C EXP
log P (octanol-water) 4.22 (none) EXP
Water Solubility 7.06 mg/L 37 EXP
Vapor Pressure 1.03E-08 mm Hg 25 EST
Henry's Law Constant 1.17E-08 atm-m3/mole 25 EST
Atmospheric OH Rate Constant 1.20E-10 cm3/molecule-sec 25 EST
Toxicity:
Organism Test Type Route Reported Dose (Normalized Dose) Effect Source
mouse LD intraperitoneal > 200mg/kg (200mg/kg) Journal of Medicinal Chemistry. Vol. 11, Pg. 117, 1968.


Contents

Chemistry

Like other steroids, pregnenolone consists of four interconnected cyclic hydrocarbons. 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
Production of Pregnenolone from Cholesteol and further metabolism
Image:Reaction-Pregnenolone-Progesterone2.png
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 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 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 neurosteroids that are found in high concentrations in certain areas in the brain, and are synthesized there. Neurosteroids affect synaptic functioning, are neuroprotective, and enhance myelinization. Pregnenolone and its sulfate ester are under investigation for their potential to improve cognitive and memory functioning.<ref>Vallée M, Mayo W, Le Moal M (2001). "Role of pregnenolone, dehydroepiandrosterone and their sulfate esters on learning and memory in cognitive aging.". Brain Res Brain Res Rev 37 (1-3): 301–12. doi:10.1016/S0165-0173(01)00135-7. PMID 11744095. </ref>

Additional images

Steroidogenesis.svg

Steroidogenesis

Cholesterol.svg

Cholesterol

Progesterone-2D-skeletal.png

Progesterone

References

Unknown extension tag "references"

Template:Steroids

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