Human Endogenous Metabolite
DHEAS targets multiple receptors and molecular pathways. It acts as a non-competitive antagonist of the GABAA receptor, inhibiting chloride influx, and also possesses agonist activity at the sigma-1 (σ1) receptor, which enhances NMDA receptor activity via the σ1 receptor. It indirectly targets PPARalpha, NF-kappaB, and other nuclear receptors, mediating anti-inflammatory and anti-glucocorticoid effects. Additionally, DHEAS serves as a circulating prohormone for the biosynthesis of active steroid hormones via metabolic conversion.

Dehydroepiandrosterone sulfate (DHEAS) is the most abundant circulating steroid in human, with the highest concentrations between age 20 and 30, but displaying a significant decrease with age. Many beneficial functions are ascribed to DHEAS. Nevertheless, long-term studies are very scarce concerning the intake of DHEAS over several years, and molecular investigations on DHEAS action are missing so far. In this study, the role of DHEAS on the first and rate-limiting step of steroid hormone biosynthesis was analyzed in a reconstituted in vitro system, consisting of purified CYP11A1, adrenodoxin and adrenodoxin reductase. DHEAS enhances the conversion of cholesterol by 26%. Detailed analyses of the mechanism of DHEAS action revealed increased binding affinity of cholesterol to CYP11A1 and enforced interaction with the electron transfer partner, adrenodoxin. Difference spectroscopy showed K(d)-values of 40 ± 2.7 µM and 24.8 ± 0.5 µM for CYP11A1 and cholesterol without and with addition of DHEAS, respectively. To determine the K(d)-value for CYP11A1 and adrenodoxin, surface plasmon resonance measurements were performed, demonstrating a K(d)-value of 3.0 ± 0.35 nM (with cholesterol) and of 2.4 ± 0.05 nM when cholesterol and DHEAS were added. Kinetic experiments showed a lower Km and a higher kcat value for CYP11A1 in the presence of DHEAS leading to an increase of the catalytic efficiency by 75%. These findings indicate that DHEAS affects steroid hormone biosynthesis on a molecular level resulting in an increased formation of pregnenolone. [1]

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DHEAS exhibits diverse in vitro activities. It partially penetrates the blood-brain barrier and inhibits GABAA receptor-mediated chloride influx while enhancing NMDA receptor activity through σ1 receptors, exerting anti-inflammatory and anti-glucocorticoid effects. It also increases convulsive sensitivity. In human granulosa cells, DHEAS (20 ng/mL) increases androgen receptor, aromatase, 3beta-HSD, and COX-2 expression, while reducing estrogen receptor beta expression and increasing estrone and estradiol levels. DHEAS also inhibits pantothenate kinase (EC 2.7.1.33).

In vivo, DHEAS demonstrates significant pharmacological effects. It increases convulsive sensitivity and has been shown to exert antidepressant-like effects, anti-inflammatory actions, and neuroprotective effects in animal models. It participates in neuroprotection and regulates catecholamine secretion. DHEAS is also used in the study of depression, PTSD, and Alzheimer's disease. As a circulating reservoir, DHEAS can be converted to potent androgens and estrogens in peripheral tissues via steroidogenic enzymes. It may also be a negative predictor of cardiovascular disease mortality.

Sodium dehydroepiandrosterone sulfate is an organic sodium salt that is the monosodium salt of dehydroepiandrosterone sulfate. It has a role as a human metabolite and an EC 2.7.1.33 (pantothenate kinase) inhibitor. It contains a dehydroepiandrosterone sulfate(1-).

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A cell‑free radioligand binding assay for GABAA receptor can be performed: incubate rat brain cortical membranes (200 microg protein) with 5 nM [3H]muscimol or [3H]TBOB in 50 mM Tris-citrate buffer (pH 7.1) at 4degC for 60 min. Add DHEAS (0.1-100 microM) to test displacement. Terminate by rapid filtration through GF/B filters and count radioactivity. Non-specific binding determined with 100 microM GABA or 100 microM picrotoxin, respectively. For σ1 receptor binding, use guinea pig brain membranes and 5 nM [3H](+)-pentazocine.

For cell-based assays, culture primary preovulatory human granulosa cells in DMEM/F12 medium. Treat cells with 20 ng/mL DHEAS for 24-48 hours at 37degC. Isolate RNA and perform real-time RT-PCR to quantify expression of androgen receptor, estrogen receptors alpha/beta, progesterone receptor, aromatase, 3beta-HSD, and COX-2. Collect culture medium and measure steroid hormone levels (estrone, estradiol, progesterone, androstenedione, testosterone) by immunoassay. DHEAS treatment increases androgen receptor, aromatase, 3beta-HSD, and COX-2 expression, and elevates estrone and estradiol.

In animal models, DHEAS is administered to study its antidepressant and neuroprotective effects. A typical protocol uses male Sprague-Dawley rats (250-300 g). DHEAS is dissolved in saline and administered intraperitoneally at doses ranging from 10-50 mg/kg. For the forced swim test, DHEAS is given 30 min before testing; reduced immobility time indicates antidepressant-like effect. For neuroprotection studies, DHEAS is administered prior to induction of cerebral ischemia or neuronal injury. In post-traumatic stress disorder models, DHEAS is administered systemically, and behavioral assessments (elevated plus maze, open field test) are conducted.

Metabolism / Metabolites
Dehydroepiandrosterone sulfate (DHEAS) is the sulfate of dehydroepiandrosterone (DHEA). This conversion is reversibly catalyzed primarily in the adrenal glands, liver, and small intestine by sulfotransferase (SULT2A1). DHEA sulfate can also be reversed back to DHEA by steroid sulfatases. In the blood, most DHEA exists as DHEAS, at concentrations approximately 300 times higher than free DHEA. Orally ingested DHEA is converted to sulfate as it passes through the intestines and liver. DHEAS levels do not exhibit diurnal variation. In both men and women, the conversion of DHEAS to DHEA, and then to testosterone, requires the catalysis of 17β-hydroxysteroid dehydrogenase.

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DHEAS pharmacokinetics: The sulfate ester exhibits a long plasma half-life of approximately 10-20 hours in humans, compared to unconjugated DHEA which has a half-life of only 15-30 minutes. DHEAS circulates at concentrations 100- to 1000-fold higher than unconjugated DHEA, serving as a stable circulating reservoir. It is metabolized via desulfation to DHEA, which is then converted to active androgens and estrogens. Oral bioavailability is moderate, with peak plasma levels reached within 2-4 hours after oral administration. DHEAS is eliminated primarily via renal excretion.

Toxicity Summary
While DHEA (produced from DHEAS) primarily functions as an endogenous precursor to more potent androgens such as testosterone and dihydroxytestosterone, studies have found that DHEA itself also possesses androgenic activity, acting as a weak partial agonist with low affinity (Ki = 1 μM) for androgen receptors. DHEA has also been found to bind to and activate ERα and ERβ estrogen receptors with Ki values of 1.1 μM and 0.5 μM, respectively. When sufficient amounts of DHEAS are ingested, masculinizing effects can occur. DHEAS is considered a precursor to androgenic steroids because testosterone (and its products) is an androgen or male hormone. In both men and women, the conversion of DHEAS to testosterone requires the catalysis of 17β-hydroxysteroid dehydrogenase. Testosterone plays a crucial role in the development of male reproductive tissues such as the testes and prostate and promotes the development of secondary sexual characteristics, such as muscle growth, bone mass increase, and body hair growth. High levels of testosterone can lead to masculinization in women or precocious puberty in boys. High levels of testosterone over a long period in adults can lower levels of high-density lipoprotein (HDL, or "good cholesterol"), increasing the risk of heart attacks, strokes, and blood clots. Gynecomastia (often caused by excessively high levels of circulating estradiol) is due to aromatase promoting the conversion of testosterone into estradiol. Men may also experience decreased libido and temporary infertility.

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Female TDLo IV 4 mg/kg Gastrointestinal: Nausea or vomiting; Skin and appendages (skin): Other dermatitis: After systemic exposure, Japanese Medical Bulletin, 18(5)(10), 1981
Oral LD50 in rats >10 gm/kg, Japanese Pharmacy, 6(687), 1982
Intraperitoneal LD50 in rats 523 mg/kg Behavior: Changes in sleep duration (including changes in righting reflex); Behavior: Ataxia, Kiso and Clinical, 10(1852), 1976
Intravenous LD50 in rats 468 mg/kg Behavior: Seizures or effects on epileptic threshold; Behavior: Ataxia; Lung, chest or respiratory: Dyspnea Kiso to Rinsho. Clinical Report, 10(1852), 1976
Vaginal LD50 in rats >500 mg/kg Oyo Yakuri. Pharmacology, 48(189), 1994

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DHEAS is generally well-tolerated at physiological levels. Long-term safety studies in humans have shown that DHEA/DHEAS supplementation (25-50 mg/day) is generally safe with mild androgenic side effects (acne, hirsutism) as the most common adverse events. No significant toxicity was reported in animal studies at doses up to 100 mg/kg. Contraindications include hormone-sensitive cancers (breast, prostate). In high doses, it may increase convulsive sensitivity. For laboratory handling, DHEAS is a mild irritant; standard safety precautions (gloves, lab coat) are recommended.

[1]. Dehydroepiandrosterone Sulfate (DHEAS) Stimulates the First Step in the Biosynthesis of Steroid Hormones. PLoS One. 2014 Feb 21;9(2):e89727.

Dehydroepiandrosterone sulfate (DHEA-S) is a steroidal steroid, a 3-sulfonoxy derivative of dehydroepiandrosterone. It is an EC 2.7.1.33 (pantothenic acid kinase) inhibitor and a metabolite in humans and mice. It is a steroidal steroid and a 17-oxosteroid. Its function is related to dehydroepiandrosterone. It is the conjugate acid of dehydroepiandrosterone sulfate (1-). Dehydroepiandrosterone sulfate is the major steroidal steroid of the fetal adrenal gland. DHEA-S is the major adrenal androgen, co-secreted with cortisol under the regulation of adrenocorticotropic hormone (ACTH) and prolactin. Hyperprolactinemia can lead to elevated DHEA-S levels. Studies have reported the presence of dehydroepiandrosterone sulfate in both humans and honeybees. Dehydroepiandrosterone sulfate (DHEAS) is the sulfated form of dehydroepiandrosterone (DHEA). This sulfation reaction is reversibly catalyzed primarily by sulfotransferase 2A1 (SULT2A1) in the adrenal glands, liver, and small intestine. Most DHEA in the blood exists as DHEAS, at levels approximately 300 times higher than free DHEA. Orally ingested DHEA is converted to sulfate as it passes through the intestines and liver. DHEA levels typically peak in the morning, while DHEAS levels do not exhibit diurnal variation. From a practical standpoint, DHEAS measurement is superior to DHEA because DHEAS levels are more stable. DHEA (a precursor to DHEAS) is a natural steroid hormone synthesized from cholesterol by the adrenal glands, gonads, adipose tissue, brain, and skin (through autocrine mechanisms). DHEA is a precursor to androstenedione, which can be further converted into the androgens testosterone and the estrogens estrone and estradiol. DHEA is also a potent σ-1 receptor agonist. DHEAS can serve as a precursor to testosterone, androstenedione, estradiol, and estrone. Serum dehydroepiandrosterone sulfate (DHEA-S) is a classic marker of adrenal gland development, reflecting individual hormone levels. DHEA-S is an endogenously produced sex steroid believed to have anti-aging effects. It is also negatively correlated with the development of atherosclerosis (A3325, A3326, A3327). DHEA-S is the primary adrenal androgen, co-secreted with cortisol under the regulation of adrenocorticotropic hormone (ACTH) and prolactin. Hyperprolactinemia can lead to elevated DHEA-S levels. DHEA-S is the circulating form of a major C19 steroid primarily produced by the adrenal cortex. DHEA-S is a precursor to testosterone, androstenedione, and estradiol.

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Drug Indications
It has been studied for the treatment of asthma, burns, and burn infections.

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Mechanism of Action
Low levels of dehydroepiandrosterone sulfate (DHEA-S) are associated with adverse levels of several strong risk factors for cardiovascular disease, such as blood lipids and dyslipidemia (a component of metabolic syndrome) and insulin levels. DHEA-S deficiency is a risk factor for obesity and insulin resistance, but it is unclear whether this potential effect exists independently.

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DHEAS is not approved as a therapeutic drug in most countries, although prasterone (DHEA) is available as a dietary supplement in the US and is approved for vaginal administration in certain formulations for dyspareunia. DHEAS is widely used as an analytical standard for LC-MS/MS calibration and as a research tool for studying steroid hormone pathways, neurosteroid signaling, and metabolic disorders. It is also used in the diagnosis of adrenal insufficiency and polycystic ovary syndrome (PCOS) as a clinical biomarker. Molecular formula: C19H27NaO5S, MW: 390.47 g/mol. For research use only.

C19H27NAO5S

390.47

390.147

1099-87-2

12594

Solid powder

148-149 °C (dec.)(lit.)

10 ° (C=4, MeOH)

4.444

1

5

2

25

721

6

C[C@@]12CC[C@@H](CC2=CC[C@H]3[C@@H]4CCC(=O)[C@@]4(C)CC[C@@H]31)OS(=O)(=O)[O-].[Na+]

CZWCKYRVOZZJNM-USOAJAOKSA-N

InChI=1S/C19H28O5S/c1-18-9-7-13(24-25(21,22)23)11-12(18)3-4-14-15-5-6-17(20)19(15,2)10-8-16(14)18/h3,13-16H,4-11H2,1-2H3,(H,21,22,23)/t13-,14-,15-,16-,18-,19-/m0/s1

[(3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-oxo-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-yl] hydrogen sulfate

Sodium prasterone sulfate; sodium prasterone sulfate; Prasterone sodium sulfate; 1099-87-2; Teloin; Sodium dehydroepiandrosterone sulfate; Mylis; Dehydroepiandrosterone sulfate sodium salt; Dehydroepiandrosterone sulfate sodium;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : 100 mg/mL (256.10 mM; with sonication)
H2O : 10 mg/mL (25.61 mM; with sonication)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.33 mM)(Saturation unknown) in 10% DMSO 40% PEG300 5% Tween-80 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution, add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix well; then add 50 μL Tween-80 to the above system and mix well; then add 450 μL saline to make up to 1 mL.
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (5.33 mM)(Saturation unknown) in 10% DMSO 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution, add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD in saline and mix well.
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (5.33 mM)(Saturation unknown) in 10% DMSO 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution, add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL corn oil and mix well.

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 (Please use freshly prepared in vivo formulations for optimal results.)