Dehydroepiandrosterone sulfate

DHEA sulfate as a hormone

Dehydroepiandrosterone sulfate, abbreviated as DHEA sulfate or DHEA S, also known as androstenolone sulfate, is an endogenous androstane steroid that is produced by the adrenal cortex. However, DHEA S retains activity as a neurosteroid and neurotrophin. It has been found to act as a positive allosteric modulator of the NMDA receptor (50 nM–1 μM), negative allosteric modulator of the GABAA and glycine receptors, and weak agonist of the sigma 1 receptor (Kd > 50 μM). In addition, DHEA S has been found to directly bind to and activate the TrkA and p75NTR – receptors of neurotrophins like nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) – with high affinity (around 5 nM).

Although DHEA S itself is hormonally inert, it has been thought that it can be converted back into DHEA, which is weakly androgenic and estrogenic, and that DHEA in turn can be transformed into more potent androgens like testosterone and dihydrotestosterone (DHT) as well as estrogens like estradiol. As such, it has been thought that DHEA S is a prohormone with the potential for androgenic and estrogenic effects.

DHEA S has also been found to inhibit the TRPV1 and TRPC5 transient receptor potential channels and to inhibit the P2X receptor.]]

DHEA and DHEA S are produced in the zona reticularis of the adrenal cortex under the control of adrenocorticotropic hormone (ACTH). DHEA is synthesized from cholesterol via the enzymes cholesterol side chain cleavage enzyme (CYP11A1; P450scc) and 17α hydroxylase/17,20 lyase (CYP17A1), with pregnenolone and 17α hydroxypregnenolone as intermediates. Then, DHEA S is formed by sulfation of DHEA at the C3β position via the sulfotransferase enzymes SULT2A1 and to a lesser extent SULT1E1. Whereas DHEA is derived mostly from the adrenal cortex but is also secreted to a lesser extent by the gonads (10%), DHEA S is almost exclusively produced and secreted by the adrenal cortex, with 95 to 100% originating from the adrenal cortex in women. Approximately 10 to 15 mg of DHEA S is secreted by the adrenal cortex per day in young adults.

Unlike DHEA, which is weakly bound to albumin, DHEA S is strongly bound to albumin (i. e., with very high affinity), and this is the reason for its much longer comparative terminal half life. In contrast to DHEA, DHEA S is not bound to any extent to sex hormone binding globulin (SHBG). Whereas DHEA easily crosses the blood–brain barrier into the central nervous system, DHEA S poorly crosses the blood–brain barrier.

DHEA S can be converted back into DHEA via steroid sulfatase (STS). DHEA S serves as a depot for potent androgens like testosterone and dihydrotestosterone in prostate cancer, which fuel the growth of this cancer. The elimination half life of DHEA S is 7 to 10 hours, which is far longer than that of DHEA, which has an elimination half life of only 15 to 30 minutes.

As the sodium salt, prasterone sodium sulfate, DHEA S is used as a pharmaceutical drug in Japan in the treatment of insufficient cervical ripening and cervical dilation during childbirth.

DHEA S levels above 1890 μM or 700 to 800 μg/dL are highly suggestive of adrenal dysfunction because DHEA S is made by the adrenal glands and also synthesized in the brain. The presence of DHEA S is therefore used to rule out ovarian or testicular origin of excess androgen. Women with hirsutism commonly present with mildly elevated DHEA S levels. Common etiologies for hirsutism include ovarian dysfunction (polycystic ovary syndrome) and adrenal dysfunction (congenital adrenal hyperplasia, cushing's syndrome, androgen secreting tumors); 90% of these cases are caused by PCOS or are idiopathic in nature. However, severely increased DHEA S levels (>700 μg/dL) necessitate further workup and are almost stem from benign or malignant adrenal alterations.

DHEA S, also known as androst 5 en 3β ol 17 one 3β sulfate, is a naturally occurring androstane steroid and the C3β sulfate ester of DHEA.