Pregnenolone sulfate
Skeletal formula
Ball-and-stick model of pregnenolone sulfate as an anion
Names
Preferred IUPAC name
(1S,3aS,3bS,7S,9aR,9bS,11aS)-1-Acetyl-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[a]phenanthren-7-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
3D model (JSmol)
ChEMBL
ChemSpider
UNII
  • 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 ☒N
    Key: DIJBBUIOWGGQOP-QGVNFLHTSA-N ☒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
  • 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
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).
☒N verify (what is checkY☒N ?)

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]

Biological activity

Pregnenolone sulfate is a neurosteroid with excitatory effects in the brain, acting as a potent negative allosteric modulator of the GABAA 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.
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.

Chemistry

See also: List of neurosteroids

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. ^ a b c d e Harteneck C (2013). "Pregnenolone sulfate: from steroid metabolite to TRP channel ligand". Molecules. 18 (10): 12012–28. doi:10.3390/molecules181012012. PMC 6270300. PMID 24084011.
  2. ^ a b c d 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.