Pregnenolone sulfate

Pregnenolone sulfate (PS, PREGS) is an endogenous excitatory neurosteroid that is synthesized from pregnenolone.[1][2] It is known to have cognitive and memory-enhancing, antidepressant, anxiogenic, and proconvulsant effects.[2]

Pregnenolone sulfate

Names
IUPAC name [(3S,8S,9S,10R,13S,14S,17S)-17-acetyl-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl] hydrogen sulfate
Other names Pregn-sulf; Pregnenolone monosulfate; Pregnenolone hydrogen sulfate; Pregnenolone 3β-sulfate; 5-Pregnen-3β-ol-20-one sulfate; (3β)-3-(Sulfooxy)pregn-5-en-20-one; 5-Pregnen-3β-sulfate-20-one; 20-Oxo-5-pregnen-3β-yl sulfate
Identifiers
CAS Number	1247-64-9
3D model (JSmol)	Interactive image
ChEMBL	ChEMBL141573
ChemSpider	94802
IUPHAR/BPS	4290
PubChem CID	105074
UNII	04Y4D91RG0
CompTox Dashboard (EPA)	DTXSID60924910
InChI InChI=1S/C21H32O5S/c1-13(22)17-6-7-18-16-5-4-14-12-15(26-27(23,24)25)8-10-20(14,2)19(16)9-11-21(17,18)3/h4,15-19H,5-12H2,1-3H3,(H,23,24,25)/t15-,16-,17+,18-,19-,20-,21+/m0/s1 Key: DIJBBUIOWGGQOP-QGVNFLHTSA-N InChI=1/C21H32O5S/c1-13(22)17-6-7-18-16-5-4-14-12-15(26-27(23,24)25)8-10-20(14,2)19(16)9-11-21(17,18)3/h4,15-19H,5-12H2,1-3H3,(H,23,24,25)/t15-,16-,17+,18-,19-,20-,21+/m0/s1 Key: DIJBBUIOWGGQOP-QGVNFLHTBX
SMILES CC(=O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CC=C4[C@@]3(CC[C@@H](C4)OS(=O)(=O)O)C)C
Properties
Chemical formula	C21H32O5S
Molar mass	396.54 g·mol^−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Biological activity

Pregnenolone sulfate is a neurosteroid with excitatory effects in the brain, acting as a potent negative allosteric modulator of the GABA_A receptor and a weak positive allosteric modulator of the NMDA receptor.[1][2] To a lesser extent, it also acts as a negative allosteric modulator of the AMPA, kainate, and glycine receptors,[3][4] and may interact with the nACh receptors as well.[1] In addition to its effects on ligand-gated ion channels, pregnenolone sulfate is an agonist of the sigma receptor,[2] as well as an activator of the TRPM1 and TRPM3 channels.[1] It may also interact with potassium channels and voltage-gated sodium channels[1] and has been found to inhibit voltage-gated calcium channels.[5]

Biochemistry

Steroidogenesis, with pregnenolone, the precursor of pregnenolone sulfate, at top left.

Biosynthesis

Pregnenolone sulfate is synthesized from pregnenolone via sulfation. Pregnenolone itself is produced from cholesterol via cholesterol side-chain cleavage enzyme.

Distribution

Pregnenolone sulfate does not cross the blood–brain barrier.[6][7]

Chemistry

Pregnenolone sulfate, also known as pregn-5-en-3β-ol-20-one 3β-sulfate, is a naturally occurring pregnane steroid and a derivative of cholesterol. It is the C3β sulfate ester of pregnenolone. A closely related steroid is dehydroepiandrosterone sulfate (DHEA-S), which is the C3β sulfate ester of dehydroepiandrosterone (DHEA).

References

1. Harteneck C (2013). "Pregnenolone sulfate: from steroid metabolite to TRP channel ligand". Molecules. 18 (10): 12012–28. doi:10.3390/molecules181012012. PMID 24084011.
2. Reddy DS (2010). "Neurosteroids: endogenous role in the human brain and therapeutic potentials". Prog. Brain Res. 186: 113–37. doi:10.1016/B978-0-444-53630-3.00008-7. PMC 3139029. PMID 21094889.
3. Park-Chung M, Wu FS, Farb DH (July 1994). "3 alpha-Hydroxy-5 beta-pregnan-20-one sulfate: a negative modulator of the NMDA-induced current in cultured neurons". Mol. Pharmacol. 46 (1): 146–50. PMID 7520124.
4. Yaghoubi N, Malayev A, Russek SJ, Gibbs TT, Farb DH (August 1998). "Neurosteroid modulation of recombinant ionotropic glutamate receptors". Brain Res. 803 (1–2): 153–60. doi:10.1016/s0006-8993(98)00644-1. PMID 9729352.
5. Mellon SH (2007). "Neurosteroid regulation of central nervous system development". Pharmacol. Ther. 116 (1): 107–24. doi:10.1016/j.pharmthera.2007.04.011. PMC 2386997. PMID 17651807.
6. Jong Rho; Raman Sankar; Carl E. Stafstrom (18 June 2010). Epilepsy: Mechanisms, Models, and Translational Perspectives. CRC Press. pp. 479–. ISBN 978-1-4200-8560-0.
7. CIBA Foundation Symposium (30 April 2008). Steroids and Neuronal Activity. John Wiley & Sons. pp. 101–. ISBN 978-0-470-51399-6.