| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
As a 5β-reduced metabolite, tetrahydrocortisone does not possess significant agonistic activity at the glucocorticoid receptor (GR). Research has shown that 5β-reduced metabolites bind to GR with much weaker affinity compared to 5α-reduced metabolites, with dissociation constants (Kd) in the micromolar rather than nanomolar range. Tetrahydrocortisone primarily participates in metabolism as the product of AKR1D1 (5β-reductase), an enzyme that regulates glucocorticoid availability and GR activation by reducing glucocorticoids to 5β-tetrahydro metabolites. Unlike 5α-reduced metabolites, 5β-tetrahydrocortisone cannot effectively bind to and activate GR due to the cis-configuration of its A/B ring junction.
Tetrahydrocortisone does not have a direct pharmacological target as it is an inactive metabolite. It is formed from cortisone through reduction by 5α-reductase. The compound serves as a biomarker for glucocorticoid metabolism and AKR1D1 activity. It can be used for mechanistic studies of metabolic diseases such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. As a metabolite, its levels reflect the activity of the glucocorticoid metabolic pathway. |
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| ln Vitro |
Tetrahydrocortisone itself does not possess significant pharmacological activity in vitro. As a 5β-reduced metabolite, it stands in sharp contrast to 5α-reduced metabolites: studies have shown that 5α-tetrahydro metabolites (such as 5α-tetrahydrocorticosterone) effectively bind to and activate GR, whereas 5β-tetrahydro metabolites exhibit very low affinity for GR. In vitro, 5β-reduced metabolites poorly compete with dexamethasone for GR binding sites at nanomolar concentrations, with Kd values typically in the micromolar range, approximately 10 to 30 times higher than those of 5α-metabolites. Therefore, tetrahydrocortisone is not considered an agonist or antagonist in conventional GR activity assays.
In vitro, Tetrahydrocortisone is not biologically active as it is an inactive metabolite. It is used as a reference standard and biomarker in analytical assays. The compound can be detected and quantified in biological samples using HPLC or mass spectrometry. Its levels in vitro reflect the activity of 5α-reductase and glucocorticoid metabolism. The compound is not used in functional cellular assays due to its lack of biological activity. |
| ln Vivo |
Tetrahydrocortisone is one of the major terminal products of glucocorticoid inactivation metabolism in vivo. A classic 1968 human study showed that after intravenous injection of ³H-labeled tetrahydrocortisone, approximately 81% of radioactivity was recovered in urine within 48 hours, with the principal excretory product being tetrahydrocortisone itself (approximately half of the glucuronide fraction), along with its conversion product β-cortolone (12-31%). The study also found that approximately 20% of urinary tetrahydrocortisol originated from the reduction of tetrahydrocortisone. In clinical research, the urinary ratio of tetrahydrocortisone (THE) to tetrahydrocortisol (THF) is widely used as a biomarker to assess 11β-hydroxysteroid dehydrogenase (11β-HSD) activity and the metabolic status of glucocorticoids in vivo.
In vivo, Tetrahydrocortisone is a terminal metabolite of glucocorticoid metabolism. It is excreted in urine and serves as a biomarker for cortisol metabolism. Its levels can be used to assess the activity of 5α-reductase and AKR1D1 in vivo. The compound has been studied in the context of metabolic diseases such as NAFLD and type 2 diabetes. It is not administered as a therapeutic agent but measured as a metabolic marker. |
| Enzyme Assay |
The classic method for determining the binding affinity of tetrahydrocortisone for the glucocorticoid receptor employs a radioligand competitive binding assay. The brief protocol is as follows: Prepare cytosol or membrane homogenates from rat hepatocytes or cell lines expressing human GR. Mix a fixed concentration of radiolabeled ligand (e.g., ³H-dexamethasone, approximately 1-10 nM) with serial dilutions of tetrahydrocortisone (concentration range 10⁻¹⁰ to 10⁻⁵ M), add the receptor protein, and incubate at 4°C for 12-24 hours to reach equilibrium. After incubation, adsorb unbound free ligand using dextran-coated charcoal (DCC) suspension, centrifuge at high speed, and measure radioactivity in the supernatant using a liquid scintillation counter. Generate a competition binding curve by nonlinear regression analysis to calculate the IC₅₀ (concentration required to inhibit 50% of radioligand binding), and convert to the inhibition constant (Ki) using the Cheng-Prusoff equation.
The cell-free assay for Tetrahydrocortisone involves its detection and quantification in biological samples. HPLC or LC-MS/MS methods are used to measure Tetrahydrocortisone levels in urine, plasma, or tissue extracts. The compound serves as a reference standard for method development and validation. Its chemical identity is confirmed by comparison with authentic standards. These assays are used for studying glucocorticoid metabolism and related disorders. |
| Cell Assay |
In cellular studies, the metabolic transformation of tetrahydrocortisone can be assessed using human hepatoma cell lines such as HepG2. A typical protocol is as follows: Seed HepG2 cells at a density of 5×10⁵ cells per well in 6-well plates and culture at 37°C in 5% CO₂ for 24 hours until adherence. Prepare serial concentrations (1-50 μM) of tetrahydrocortisone in serum-free medium (prepare stock solution in DMSO, then dilute with culture medium to working concentration) and add to cells for 6-24 hours of treatment. Collect cell culture supernatant and cell lysate, purify via solid-phase extraction (SPE), and detect the formation of metabolites inside cells or in culture medium using LC-MS/MS. MTT or CCK-8 assays can be used to evaluate the impact of the compound on cell viability.
For in vitro cellular assays, Tetrahydrocortisone is not typically used due to its lack of biological activity. It may be used as a reference standard in analytical assays. When studying glucocorticoid metabolism, cells may be treated with cortisone and the production of Tetrahydrocortisone measured. This approach is used to assess 5α-reductase activity in cell culture models. The compound is not used in functional assays due to its inactivity. |
| Animal Protocol |
Tetrahydrocortisone is primarily used as a metabolite marker in animal studies, with its in vivo generation studied following administration of precursor drugs. A typical experimental protocol is as follows: Use male SD rats (body weight 180-220 g), administer hydrocortisone or cortisone acetate via tail vein injection (1-5 mg/kg) or oral gavage (5-20 mg/kg), then collect blood samples at various time points (0, 1, 2, 4, 8, 12, 24 hours), along with 24-hour urine samples. Plasma is separated by centrifugation and purified by solid-phase extraction; urine samples are directly analyzed after appropriate dilution. Quantify metabolites including tetrahydrocortisone using validated LC-MS/MS methods, plot time-concentration curves, and calculate pharmacokinetic parameters. In a three-dimensional human liver bioreactor model, following hydrocortisone (100 nM) circulation for 2 days, Phase I metabolit
In vivo animal studies for Tetrahydrocortisone involve measuring its levels as a biomarker of glucocorticoid metabolism. Animal models of metabolic diseases such as NAFLD and type 2 diabetes are used. Urine and plasma samples are collected and analyzed for Tetrahydrocortisone levels using LC-MS/MS. The compound's levels are correlated with disease progression and treatment effects. These studies help understand the role of glucocorticoid metabolism in disease. |
| ADME/Pharmacokinetics |
Tetrahydrocortisone is not an active drug administered directly but rather a terminal metabolite of glucocorticoid metabolism in vivo. In humans, hydrocortisone is metabolized in the liver to tetrahydrocortisone via sequential action of 5β-reductase (AKR1D1) and 3α-hydroxysteroid dehydrogenase; this compound is subsequently conjugated with glucuronic acid to form tetrahydrocortisone-3-glucuronide, ultimately excreted in urine via the kidneys. In a three-dimensional human liver bioreactor model, the half-life of hydrocortisone was 23.03 hours with an elimination rate constant of 0.03 hour⁻¹; Phase I metabolites including tetrahydrocortisone accounted for 8-10% of drug loss, while Phase II metabolites (including glucuronides of tetrahydrocortisol and tetrahydrocortisone) accounted for 45-52%. The calculated LogP value of tetrahydrocortisone is approximately 2.1, indicating moderate lipophilicity.
Pharmacokinetic properties of Tetrahydrocortisone include a molecular weight of 364.48 g/mol and molecular formula C21H32O5. The compound has a melting point of 227°C. As a metabolite, its pharmacokinetics reflect the formation and elimination of cortisone metabolites. It is excreted in urine as a terminal metabolite. The compound is typically stored at appropriate conditions as a reference standard. |
| Toxicity/Toxicokinetics |
As an endogenous inactivated metabolite of cortisone and hydrocortisone, this compound is present in human blood and urine under normal physiological conditions and is generally not considered to have significant toxicity. Due to the complete absence of the Δ⁴-3-keto structure required for glucocorticoid activity and the cis-configuration of its A/B ring junction, 5β-tetrahydrocortisone cannot effectively activate the glucocorticoid receptor and therefore does not cause the typical adverse reactions associated with glucocorticoid excess (such as immunosuppression, hyperglycemia, osteoporosis, etc.). In laboratory use, this compound is for research use only and should be handled following standard operating procedures, avoiding inhalation, ingestion, or skin contact.
The toxicity profile of Tetrahydrocortisone is not relevant as it is an inactive metabolite and not administered as a therapeutic agent. As a naturally occurring metabolite, it is not expected to be toxic. The compound is used as a reference standard and biomarker in research applications. Standard safety precautions should be followed when handling this compound as a chemical reference standard. It is intended for research use only. |
| References | |
| Additional Infomation |
Urocortisone is a 21-hydroxysteroid.
Tetrahydrocortisone is an inactive metabolite of cortisone generated by 5α-reductase reduction. It serves as a urinary metabolite and biomarker for in vivo AKR1D1 activity and glucocorticoid metabolic status. The compound is used for mechanistic studies of metabolic diseases such as NAFLD and type 2 diabetes. Tetrahydrocortisone is not an active drug and is strictly a research tool for studying glucocorticoid metabolism. |
| Molecular Formula |
C21H32O5
|
|---|---|
| Molecular Weight |
364.47578
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| Exact Mass |
364.225
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| Elemental Analysis |
C, 69.20; H, 8.85; O, 21.95
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| CAS # |
53-05-4
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| Related CAS # |
Tetrahydrocortisone-d5;Tetrahydrocortisone-d6;Tetrahydrocortisone acetate;17736-20-8
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| PubChem CID |
5866
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| Appearance |
White to off-white solid powder
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| Density |
1.249g/cm3
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| Boiling Point |
544.5ºC at 760mmHg
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| Melting Point |
190°C
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| Flash Point |
297.1ºC
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| Index of Refraction |
1.569
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| LogP |
1.861
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| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
26
|
| Complexity |
632
|
| Defined Atom Stereocenter Count |
8
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| SMILES |
C[C@]12CC[C@H](C[C@H]1CC[C@@H]3[C@@H]2C(=O)C[C@]4([C@H]3CC[C@@]4(C(=O)CO)O)C)O
|
| InChi Key |
SYGWGHVTLUBCEM-ZIZPXRJBSA-N
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| InChi Code |
InChI=1S/C21H32O5/c1-19-7-5-13(23)9-12(19)3-4-14-15-6-8-21(26,17(25)11-22)20(15,2)10-16(24)18(14)19/h12-15,18,22-23,26H,3-11H2,1-2H3/t12-,13-,14+,15+,18-,19+,20+,21+/m1/s1
|
| Chemical Name |
(3R,5R,8S,9S,10S,13S,14S,17R)-3,17-dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-2,3,4,5,6,7,8,9,12,14,15,16-dodecahydro-1H-cyclopenta[a]phenanthren-11-one
|
| Synonyms |
TETRAHYDROCORTISONE; Urocortisone; 53-05-4; 5HF9TM2D15; NSC-76984; .
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~137.18 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (3.43 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.25 mg/mL (3.43 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 is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 1.25 mg/mL (3.43 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7436 mL | 13.7182 mL | 27.4363 mL | |
| 5 mM | 0.5487 mL | 2.7436 mL | 5.4873 mL | |
| 10 mM | 0.2744 mL | 1.3718 mL | 2.7436 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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