Pregnenolone

Pregnenolone

File:Pregnenolone.png
Systematic (IUPAC) name
3β-hydroxypregn-5-en-20-one
Identifiers
CAS Number	145-13-1
ATC code	none
PubChem	CID 8955
IUPHAR/BPS	2376
DrugBank	EXPT02608
Chemical data
Formula	C21H32O2
Molar mass	316.483 g/mol[[]]
(verify)

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 GABA_A antagonist and increases neurogenesis in the hippocampus.

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

File:DHEA1.svg

Production of Pregnenolone from Cholesterol and further metabolism

File: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 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 corticosteroids are also derived from progesterone or its derivatives.

• 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.

• 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.
Pregnenolone sulfate was shown to activate the Transient Receptor Potential M3 ion channel in hepatocytes and pancreatic islets causing calcium entry and subsequent insulin release.

Additional images

File:Steroidogenesis.svg

Steroidogenesis, showing pregnenolone near top left.

• Cholesterol.svg

  Cholesterol

• Progesterone-2D-skeletal.png

  Progesterone

References

ca:Pregnenolona vi:Pregnenolone