dehydroepiandrosterone

The dehydroepiandrosterone (DHEA) is a multi-functional steroid that has been implicated in a broad range of biological effects in humans and other mammals.

Together with its sulfate ester (DHEA-S), it is the most abundant steroid in humans.

DHEA is produced by adrenal glands, but also sythesized de novo in the brain.

DHEA acts on the androgen receptor both directly and through its metabolites, which include androstenediol and androstendione, which can undergo further conversion to produce the androgen testosterone and the estrogens estrone and estradiol.

DHEA is also a potent sigma-1 agonist. It is considered a neurosteroid.

Biosynthesis

DHEA is produced from cholesterol through two cytochrome P450 enzymes. Cholesterol is converted to pregnenolone by the enzyme P450 scc (side chain cleavage); then another enzyme, CYP17A1, converts pregnenolone to 17α-Hydroxypregnenolone and then to DHEA.

Dehydroepiandrosterone sulfate

Dehydroepiandrosterone sulfate (DHEAS) is the sulfated version of DHEA. This conversion is reversibly catalyzed by sulfotransferase (SULT2A1) primarily in the adrenals, the liver, and small intestine. In the blood, most DHEA is found as DHEAS with levels that are about 300 times higher than those of free DHEA. Orally ingested DHEA is converted to its sulfate when passing through intestines and liver.

Whereas DHEA levels naturally reach their peak in the early morning hours, DHEAS levels show no diurnal variation. From a practical point of view, measurement of DHEAS is preferable to DHEA, as levels are more stable.