Endogenous Metabolite

Dehydroepiandrosterone sulfate (DHEAS) increases the length of neurites that carry the dendritic marker MAP-2 [1]. Dehydroepiandrosterone sulfate (DHEAS) has been shown to increase neuronal excitability (firing rate) when given directly to preseptopic neurons [1]. The human adrenal gland produces substantial amounts of dehydroepiandrosterone (DHEA), principally as 3-sulfoconjugated DHEA sulfate (DS), throughout intrauterine life [2]. Dehydroepiandrosterone sulfate (DHEAS) is generally non-toxic and does not cause negative effects even when administered for an extended period of time [3].

Performance is affected by long-term DHEAS treatment in a dose-dependent manner [3]. The goal of the current study was to test the hypothesis that dehydroepiandrosterone-sulfate (DHEAS), a pro-excitatory neurosteroid, could facilitate recovery of function in male rats after delayed treatment following TBI. DHEAS has been found to play a major role in brain development and aging by influencing the migration of neurons, arborization of dendrites, and formation of new synapses. These characteristics make it suitable as a potential treatment to enhance neural repair in response to CNS injury. In our study, behavioral tests were conducted concurrently with DHEAS administration (0, 5, 10, or 20 mg/kg) starting seven days post-injury (PI). These assays included 10 days of Morris Water Maze testing (MWM; 7d PI), 10 days of Greek-Cross (GC; 21d PI), Tactile Adhesive Removal task (TAR; PI days: 6, 13, 20, 27, 34), and spontaneous motor behavior testing (SMB; PI days: 2, 4, 6, 12, 19, 26, 33). Brain-injured rats showed an improvement in performance in all tasks after 5, 10, or 20 mg/kg DHEAS. The most effective dose of DHEAS in the MWM was 10 mg/kg, while in the GC it was 20 mg/kg, in TAR 5 mg/kg, and all doses, except for vehicle, were effective at reducing injury-induced SMB hyperactivity. In no task did DHEAS-treated animals perform worse than the injured controls. In addition, DHEAS had no significant effects on behavioral performance in the sham-operates. These results can be interpreted to demonstrate that after a 7-day delay, the chronic administration of DHEAS to injured rats significantly improves behavioral recovery on both sensorimotor and cognitive tasks. [3]

Dehydroepiandrosterone (DHEA) is produced in prodigious quantities by the human adrenal, principally as the 3-sulfoconjugate DHEA sulfate (DS) during intrauterine life. The fetal zone and neocortex cells of the fetal adrenal express large amounts of DHEA sulfotransferase and minimal amounts, at least until very near the end of gestation, of 3beta-hydroxysteroid dehydrogenase. This pattern of enzyme expression favors substantial secretion of DHEA/DS with minimal cortisol produced; the DHEA/DS serves as the major precursor for placental estrogen formation in human pregnancy. Aside from adrenocorticotropin, other physiologic regulators of growth and steroidogenesis in the fetal adrenal have been postulated to exist, but have yet to be identified. Whereas intrauterine stressors may activate adrenal cortisol secretion, the fetal adrenal responds to many pregnancy conditions by suppressing DHEA/DS formation. After birth, the human adrenal undergoes reorganization whereby the large, inner fetal zone regresses, and DHEA/DS production is diminished. Just prior to gonadal maturation, the human adrenal undergoes morphologic and functional changes (adrenarche) that give rise to a prominent zona reticularis that is characterized by the presence of DHEA sulfotransferase, the absence of 3beta-hydroxysteroid dehydrogenase, and an enhancement of DHEA/DS production. The adrenal of the adult responds to stress in many instances like that of the fetus: increased cortisol secretion and diminished DHEA/DS secretion. The mechanisms for this divergence in the adrenocortical pathway is unknown. With aging, there is suppression of DHEA/DS secretion, possibly as the consequence of an involution of the zona reticularis, but corticosteroid production continues unabated. [2]

Animal/Disease Models: Sixty-four male SD (Sprague-Dawley) rats, approximately 90 days of age (300-400 g)[3].
Doses: 5, 10, or 20 mg/kg.
Route of Administration: subcutaneous (sc) injection starting 7 days post-surgery and 1 h prior to all behavioral testing.
Experimental Results: Dramatically effective in improving latency to reach the platform as compared to injured rats receiving vehicle.

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.

Toxicity Overview
Although 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. Long-term high levels of testosterone in adults can lower levels of high-density lipoprotein cholesterol (good cholesterol), increasing the risk of heart attack, stroke, 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. Health Effects: Some researchers believe that DHEAS supplements may actually increase the risk of breast cancer, prostate cancer, heart disease, diabetes, and stroke. DHEAS may stimulate the growth of tumors in certain hormone-sensitive cancers, such as certain types of breast cancer, uterine cancer, and prostate cancer. DHEAS may worsen prostate swelling in men with benign prostatic hyperplasia (BPH, or enlarged prostate). High doses of DHEAS may cause symptoms in women such as aggression, irritability, sleep disturbances, and increased body or facial hair. It may also cause amenorrhea and lower levels of high-density lipoprotein (“good” cholesterol), thus increasing the risk of heart disease. Other reported side effects include acne, heart rhythm disturbances, liver problems, hair loss (dandruff), and oily skin. In women, DHEAS may cause breast reduction, voice deepening, vulvar enlargement, menstrual irregularities, oily skin, and abnormal hair growth. In men, DHEAS may cause aggression, breast tenderness or enlargement, testicular atrophy, and urinary urgency. DHEAS may interfere with the way the body processes certain substances using the liver's cytochrome P450 enzyme system. Long-term high levels of dehydroepiandrosterone sulfate have been associated with male pseudohermaphroditism with gynecomastia.

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Route of exposure: Endogenous, ingestion

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Symptoms
In women, DHEAS may cause breast reduction, voice deepening, genital enlargement, menstrual irregularities, oily skin, and abnormal hair growth. In men, DHEAS may cause aggression, breast tenderness or enlargement, testicular atrophy, and urinary urgency.

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The intraperitoneal LD50 in mice is 655 mg/kg. Reference: Shengzhi Yu Biyun. Reproduction and Contraception., 13(414), 1993.
The intravenous LD50 in mice is 293 mg/kg. Reference: Shengzhi Yu Biyun. Reproduction and Contraception, 13(414), 1993.

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Lowest Risk Levels
Dehydroepiandrosterone sulfate levels above 1890 μmol/L or 700-800 μg/dL strongly suggest adrenal dysfunction.

[1]. Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) as neuroactive neurosteroids. Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4089-91.

[2]. Dehydroepiandrosterone and dehydroepiandrosterone sulfate production in the human adrenal during development and aging. Steroids. 1999 Sep;64(9):640-7.

[3]. The delayed administration of dehydroepiandrosterone sulfate improves recovery of function after traumatic brain injury in rats. J Neurotrauma. 2003 Sep;20(9):859-70.

Prasterone sulfate sodium is a steroidal sulfate. It is functionally associated with dehydroepiandrosterone (DHEA).
See also: Prasterone sulfate sodium (note moved to).
Dehydroepiandrosterone sulfate is a steroidal sulfate, a 3-sulfonoxy derivative of DHEA. It is an EC 2.7.1.33 (pantothenic acid kinase) inhibitor and a metabolite in humans and mice. It is a steroidal sulfate and a 17-oxosteroid. It is functionally associated with DHEA. It is the conjugate acid of DHEA sulfate (1-).
DHEA sulfate is the major steroid of the fetal adrenal gland. DHEA sulfate is the major adrenal androgen, secreted along 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 DHEA 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. DHEA-S can serve as a precursor to testosterone, androstenedione, estradiol, and estrone. Serum dehydroepiandrosterone sulfate (DHEA-S) is a classic marker of adrenal development, reflecting individual hormone levels. DHEA-S is an endogenously produced sex steroid and is considered 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, estradiol, and estrone. Drug Indications It has been studied for the treatment of asthma, burns, and burn infections. 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.

C19H27O5S-.NA+.2[H2O]

426.50004

426.169

C, 53.51; H, 7.33; Na, 5.39; O, 26.26; S, 7.52

78590-17-7

78590-17-7 (sodium);651-48-9 (free acid);

23694217

Typically exists as solid at room temperature

4.315

2

7

2

28

727

6

CC12CCC3C(C1CCC2=O)CC=C4C3(CCC(C4)OS(=O)(=O)[O-])C.O.O.[Na+]

NLNMKDUYGPNWAO-OXNWJOIVSA-M

InChI=1S/C19H28O5S.Na.2H2O/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);;2*1H2/q;+1;;/p-1/t13-,14-,15-,16-,18-,19-;;;/m0.../s1

sodium;[(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] sulfate;dihydrate

78590-17-7; Sodium prasterone sulfate dihydrate; Prasterone sulfate sodium hydrate; Prasterone sodium sulfate dihydrate; Dehydroisoandrosterone 3-sulfate sodium salt dihydrate; E1CR8487EN; DTXSID9045764; UNII-E1CR8487EN;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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