Description
7α-Hydroxypregnenolone is a neuroactive metabolite of pregnenolone. It acts as an important neuromodulator to increase locomotor activity.
Discovery
7α-Hydroxylation of pregnenolone was found in the rat brain.Subsequently, 7α-hydroxypregnenolone formation was demonstrated in the brains of various vertebrates and in the pineal glands of birds.
Gene, mRNA, and precursor
The human P450
7α gene (CYP7B1), located on chromosome 8 (8q21.3), consists of six exons.Human P450
7αmRNA has 2395bp that encodes a protein of 506 aa residues.
Biological functions
Dopamine neurons are located in the medial brain region, specifically in the TA and posterior tuberal nucleus; they project to the rostral brain region including the striatum.7α-Hydroxypregnenolone increases the concentration of dopamine in the telencephalic region including the striatum,which is known to be involved in the regulation of locomotor behavior in vertebrates. Thus, there is potential for the direct regulation of dopamine release by the action of 7α-hydroxypregnenolone synthesized in the TA. Acute stress increases the synthesis of 7α-hydroxypregnenolone through corticosterone action in newts.7α-Hydroxypregnenolone increases serotonin concentrations in the diencephalon including the DMH under stress.The pineal gland, an endocrine organ located close to the brain, is an important site of production of neurosteroids de novo from cholesterol in birds.7α-Hydroxypregnenolone is a major pineal neurosteroid that stimulates locomotor activity in juvenile chickens, connecting light-induced gene expression with locomotion.
Clinical implications
7α-Hydroxypregnenolone administration to memory impaired aged rats for 11 days enhanced spatial memory retention in the eight-arm radial-arm version of the water maze.
Uses
7α-Hydroxy Pregnenolone is a hydroxylated metabolite of Pregnenolone (P712200).
Definition
ChEBI: 7alpha-hydroxypregnenolone is a 20-oxo steroid that is pregnenolone carrying an additional hydroxy substituent at the 7alpha-position. It has a role as a rat metabolite, a marine metabolite, a nootropic agent and a dopaminergic agent. It is a 20-oxo steroid, a 3beta-hydroxy-Delta(5)-steroid, a C21-steroid and a 7alpha-hydroxy steroid. It is functionally related to a pregnenolone. It is an enantiomer of a 7beta-hydroxypregnenolone.
