(3S,8S,9R,10S,13S,14R,17R)-17-acetyl-10,13-dimethyl-3-sulfooxy-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene

Description

Pregnenolone sulfate is a neuroactive metabolite of pregnenolone. It has significant regulatory effects on the release of many important neurotransmitters such as glutamate, GABA, acetylcholine, norepinephrine, and dopamine.

Discovery

The presence of high amounts of pregnenolone sulfate in the rat brain was reported, and it was found that the concentration of this sulfated steroid was not affected by adrenalectomy and castration.

Regulation of synthesis and release

Neuropeptide Y inhibits the biosynthesis of pregnenolone sulfate in the frog hypothalamus through activation of the Y1 receptor.Gonadotropin-releasing hormone (GnRH) stimulates the biosynthesis of pregnenolone sulfate in the frog hypothalamus.

Biological functions

Pregnenolone sulfate has multiple important effects on brain functions, such as cognitive enhancing, promnesic, antistress, and antidepressant effects.Pregnenolone sulfate also has significant regulatory effects on the release of many important neurotransmitters such as glutamate, GABA, acetylcholine, norepinephrine, and dopamine.

Clinical implications

Central acetylcholine neurotransmission is known to be involved in the regulation of cognitive processes and is affected in normal aging and severely altered in human neurodegenerative pathologies such as Alzheimer’s disease.The level of acetylcholine cortical release induced by the infusion of pregnenolone sulfate was correlated to the spatial memory performance of animals.The infusion of pregnenolone sulfate stimulated the release of acetylcholine, suggesting that this effect could partly explain the memory-enhancing properties of this neurosteroid.

Definition

ChEBI: Pregnenolone sulfate is a steroid sulfate. It has a role as an EC 2.7.1.33 (pantothenate kinase) inhibitor and a human metabolite. It is functionally related to a pregnenolone. It is a conjugate acid of a pregnenolone sulfate(1-).