5a-Tetrahydrocorticosterone

5α-Tetrahydrocorticosterone (5α-THB) is a metabolite of corticosterone, a glucocorticoid hormone produced in the adrenal cortex.

Formed through 5α-reduction by 5α-reductase and further 3α-reduction by aldo-keto reductase (AKR) enzymes, 5α-THB exhibits anti-inflammatory properties with minimal metabolic side effects.

It plays a role in modulating GABA_A receptor activity, providing anxiolytic and sedative effects.

Additionally, 5α-THB levels are significant as potential biomarkers for adrenal and metabolic disorders, as well as conditions like breast cancer, aiding in disease diagnosis and monitoring.

What is 5a-Tetrahydrocorticosterone? [9.]

5α-tetrahydrocorticosterone (5α-THB) is one of the metabolites of corticosterone, a glucocorticoid hormone produced in the adrenal cortex.

Corticosterone can undergo reduction reactions in the liver to form 5α- and 5β-reduced metabolites. Specifically, corticosterone is metabolized by 5α-reductase to form 5α-THB and by 5β-reductase to form 5β-tetrahydrocorticosterone (THB).

Both of these metabolites are subsequently 3α-reduced by aldo-keto reductase (AKR) family enzymes.

The primary function of these reduction reactions is to inactivate the glucocorticoid and prepare it for excretion. The resulting tetrahydro metabolites, including 5α-THB, are excreted in urine, predominantly as glucuronide conjugates.

Physiological Functions of 5a-Tetrahydrocorticosterone [4., 6.]

5α-THB is a potential selective anti-inflammatory with reduced metabolic effects compared to hydrocortisone.

When administered systemically to mice, 5α-THB suppressed inflammation without adverse metabolic side-effects in the short term.

Topically, 5α-THB suppresses irritant dermatitis and increases expression of anti-inflammatory mediators like lipocortin and DUSP1.

In a study assessing the anti-inflammatory effects of 5a-tetrahydrocorticosterone vs. hydrocortisone on irritant dermatitis involving mice, topical 5α-THB demonstrated an ability to treat inflammatory skin conditions, especially in areas of delicate skin. [4., 6.]

5a-Tetrahydrocorticosterone as a Biomarker

5a-Tetrahydrocorticosterone (5a-THB) has gained significant attention as a potential biomarker for various diseases and conditions due to its unique properties and involvement in physiological processes.

Diseases and Conditions Associated with Altered 5a-THB Levels

Adrenal Disorders

Elevated levels of 5a-THB have been observed in patients with some forms of congenital adrenal hyperplasia (CAH), a group of inherited disorders affecting cortisol biosynthesis.

In CAH, the accumulation of steroid precursors including 5a-THB can serve as a diagnostic marker and aid in monitoring disease progression and treatment response. [7.]

Additionally, elevated 5-alpha reductase metabolites have been demonstrated in PCOS. [11.]

Metabolic Disorders [1., 3.]

Research has suggested a link between 5a-THB levels and metabolic disorders such as obesity, hypertension and diabetes.

Increased serum concentrations of 5a-THB have been associated with insulin resistance, dyslipidemia, and other metabolic abnormalities.

Monitoring 5a-THB levels may provide insights into metabolic dysregulation and aid in risk assessment and management.

Breast Cancer

Decreased levels of some steroid hormone metabolites including 5a-tetrahydrocorticosterone have been noted in premenopausal women with breast cancer. [5.]

Laboratory Testing for 5a-Tetrahydrocorticosterone

Test Information, Sample Collection and Preparation

Cortisol metabolites such as 5a-THB are often tested in the urine, commonly over 24 hours. They may also be tested in the blood.

It is important to consult with the ordering provider regarding preparation for sample collection, as certain supplements or medications may need to be avoided.

Interpreting 5a-THB Levels

Optimal Levels of 5a-THB

It is important to assess levels of adrenal hormones in the broader context of overall hormone levels.

Additionally, interpretation should take into account the presence of any symptoms of hormone excess or deficiency.

One lab reports the following optimal levels for 5a-THB: 90-380 ng/mg Creatinine/Day. [8.]

Clinical Significance of Elevated 5a-THB

Elevated levels of 5a-THB can be seen in conditions associated with increased cortisol production and adrenal activity, including Cushing syndrome, elevated cortisol output in stress or inflammation, or elevated 5alpha-reductase activity which can occur in PCOS or other conditions of hyperandrogenism. [2., 7., 11.]

Obesity and other metabolic disorders can also show high 5a-THB levels. [1., 3.]

Chronic or excessive alcohol use can also raise cortisol levels and, therefore, its metabolites including 5a-THB. [10.]

Clinical Significance of Decreased 5a-THB

Decreased levels of 5a-THB may signal decreased cortisol output due to Addison’s disease or adrenal insufficiency. It has also been seen in some women with breast cancer. [5.]

5a-Tetrahydrocorticosterone Related Biomarkers

In addition to 5a-tetrahydrocorticosterone (5a-THB), several other biomarkers are relevant in the context of diseases and conditions associated with altered 5a-THB levels.

Cortisol and Other Adrenal Hormones

Cortisol, the primary glucocorticoid hormone produced by the adrenal glands, is closely related to 5a-THB in terms of biosynthesis and metabolism.

Measuring cortisol levels alongside 5a-THB can provide valuable insights into adrenal function and the regulation of the hypothalamic-pituitary-adrenal (HPA) axis.

Other adrenal hormones, such as aldosterone and dehydroepiandrosterone (DHEA), may also be evaluated in conjunction with 5a-THB to assess adrenal disorders.

Steroid Metabolites

Several steroid metabolites including tetrahydrocortisone (THE) and tetrahydrocortisol (THF), are closely related to 5a-THB and may serve as complementary biomarkers.

These metabolites are formed through similar enzymatic pathways and can provide additional information about steroid metabolism and potential dysregulation in various disease states.

Inflammatory Markers

As 5a-THB has been implicated in the modulation of inflammatory processes, assessing inflammatory markers in conjunction with 5a-THB levels can be informative.

C-reactive protein (CRP), a widely used marker of systemic inflammation, and cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-a), may be evaluated to gain a comprehensive understanding of the inflammatory status and its relationship with 5a-THB levels.

Metabolic Markers

In the context of metabolic disorders, such as obesity and diabetes, where altered 5a-THB levels have been observed, assessing metabolic markers can provide valuable insights.

These markers may include glucose levels, lipid profiles (e.g., triglycerides, cholesterol), insulin levels, and markers of insulin resistance (e.g., HOMA-IR).

Evaluating these markers in conjunction with 5a-THB can aid in understanding the interplay between steroid metabolism and metabolic dysregulation.

Frequently Asked Questions (FAQs) on 5a-Tetrahydrocorticosterone

The FAQ section addresses common questions and concerns about 5a-Tetrahydrocorticosterone, providing clear and concise answers for better understanding.

What Is 5a-Tetrahydrocorticosterone?

5a-Tetrahydrocorticosterone is a metabolite of corticosterone, a steroid hormone produced in the adrenal glands. It plays a role in the regulation of stress response and immune function.

Why Is 5a-Tetrahydrocorticosterone Important?

5a-Tetrahydrocorticosterone is important because it serves as an indicator of adrenal gland function and can provide insights into the body's stress response.

Abnormal levels can be associated with various health conditions including adrenal disorders and chronic stress.

What Is the Function of 5a-Tetrahydrocorticosterone?

5a-Tetrahydrocorticosterone functions primarily as a metabolite in the pathway of steroid hormone synthesis. It helps regulate the body's response to stress and immune function by influencing various physiological processes.

How Is 5a-Tetrahydrocorticosterone Measured?

5a-Tetrahydrocorticosterone levels are typically measured through blood tests or urine tests. These tests are conducted in a laboratory where the samples are analyzed to determine the concentration of the metabolite.

What Are Normal Levels of 5a-Tetrahydrocorticosterone?

Normal levels of 5a-Tetrahydrocorticosterone can vary depending on factors such as age, sex, and overall health.

Reference ranges are provided by the testing laboratory and should be interpreted by a healthcare provider within the context of the patient's health status.

What Can Cause Elevated Levels of 5a-Tetrahydrocorticosterone?

Elevated levels of 5a-Tetrahydrocorticosterone can be caused by conditions such as adrenal hyperplasia, Cushing's syndrome, chronic stress, and certain medications that affect adrenal gland function.

High levels may indicate an overactive adrenal gland or excessive production of corticosterone.

What Can Cause Low Levels of 5a-Tetrahydrocorticosterone?

Low levels of 5a-Tetrahydrocorticosterone may result from adrenal insufficiency, Addison's disease, or hypothalamic-pituitary-adrenal (HPA) axis dysfunction. These conditions lead to inadequate production of adrenal hormones.

What Are the Symptoms of Abnormal 5a-Tetrahydrocorticosterone Levels?

Symptoms of abnormal 5a-Tetrahydrocorticosterone levels can vary based on whether levels are high or low.

High levels may cause symptoms such as weight gain, high blood pressure, fatigue, and muscle weakness.

Low levels may lead to symptoms like weight loss, low blood pressure, fatigue, and darkening of the skin.

How Are Abnormal Levels of 5a-Tetrahydrocorticosterone Treated?

Treatment for abnormal levels of 5a-Tetrahydrocorticosterone depends on the underlying cause.

Treatment options may include hormone replacement therapy, medications to regulate adrenal gland function, lifestyle changes to reduce stress, and addressing any underlying health conditions.

It is essential to work with a healthcare provider to develop an appropriate treatment plan.

Why Might a Doctor Order a 5a-Tetrahydrocorticosterone Test?

A doctor might order a 5a-Tetrahydrocorticosterone test to evaluate adrenal gland function, diagnose adrenal disorders such as Cushing's syndrome or Addison's disease, and monitor the body's response to stress.

It can also be part of a comprehensive hormonal evaluation for patients presenting with symptoms of adrenal imbalance.

Is the 5a-Tetrahydrocorticosterone Test Safe?

Yes, the 5a-Tetrahydrocorticosterone test is safe. The most common risk associated with the test is slight discomfort or bruising at the site where blood is drawn. Urine tests are non-invasive and generally risk-free.

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What's

5a-Tetrahydrocorticosterone

5a-Tetrahydrocorticosterone, often abbreviated as 5a-THB, is a naturally occurring hormone in your body. It's a type of steroid hormone, which means it's derived from cholesterol and plays a vital role in various bodily functions. 5a-THB is produced in your adrenal glands, small organs located above your kidneys. This hormone is part of the glucocorticoid family, which are hormones that help your body respond to stress, regulate your immune system, and maintain overall homeostasis - the state of steady internal conditions necessary for your survival. 5a-THB is also involved in the regulation of inflammation in your body. It helps to control the body's inflammatory response, which is crucial in protecting your body from harm, but also needs to be carefully regulated to prevent excessive inflammation that can lead to health problems. In summary, 5a-Tetrahydrocorticosterone is a key player in maintaining your body's balance and responding to stress, making it an essential part of your body's complex hormonal system.

If Your Levels Are High

High levels of 5a-Tetrahydrocorticosterone, or 5a-THB, could indicate that your body is under a lot of stress or dealing with inflammation. This hormone, which is made in your adrenal glands, helps your body manage stress and control inflammation. It's like your body's natural stress and inflammation manager. If you have more of it than usual, it could mean that your body is working overtime to handle stress or inflammation. This could be due to a variety of factors, such as an illness, injury, or even certain medications like corticosteroids. It's also possible that your adrenal glands are producing too much of this hormone, which could be due to a condition like adrenal hyperplasia or an adrenal tumor.

Symptoms of High Levels

Symptoms of high levels of 5a-Tetrahydrocorticosterone could include fatigue, muscle weakness, high blood pressure, increased thirst and urination, and unexplained weight loss.

If Your Levels are Low

Low levels of 5a-Tetrahydrocorticosterone, or 5a-THB, could mean your body might struggle to handle stress or maintain balance. This hormone, made in your adrenal glands, helps your body manage stress, keeps your immune system in check, and helps keep everything running smoothly. It also plays a big role in controlling inflammation, which is your body's way of protecting itself. But, if there's too much inflammation, it can cause health issues. So, if your 5a-THB levels are low, it could mean your body's not as good at controlling inflammation as it should be. Certain things like stress, certain medications like corticosteroids, or health conditions like Addison's disease, which affects your adrenal glands, could potentially cause low 5a-THB levels.

Symptoms of Low Levels

Symptoms of low levels of 5a-Tetrahydrocorticosterone could include fatigue, muscle weakness, loss of appetite, weight loss, low blood pressure, and increased susceptibility to infections due to a weakened immune response.

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See References

[1.] Ackermann D, Vogt B, Bochud M, Burnier M, Martin PY, Paccaud F, Ehret G, Guessous I, Ponte B, Pruijm M, Pechère-Bertschi A, Jamin H, Klossner R, Dick B, Mohaupt MG, Gennari-Moser C. Increased glucocorticoid metabolism in diabetic kidney disease. PLoS One. 2022 Jun 24;17(6):e0269920. doi: 10.1371/journal.pone.0269920. PMID: 35749380; PMCID: PMC9231809.

[2.] Chaudhry HS, Singh G. Cushing Syndrome. [Updated 2023 Jun 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470218/

[3.] Finken MJJ, Wirix AJG, von Rosenstiel-Jadoul IA, van der Voorn B, Chinapaw MJM, Hartmann MF, Kist-van Holthe JE, Wudy SA, Rotteveel J. Role of glucocorticoid metabolism in childhood obesity-associated hypertension. Endocr Connect. 2022 Jul 14;11(7):e220130. doi: 10.1530/EC-22-0130. PMID: 35700234; PMCID: PMC9346319.

[4.] Gastaldello A, Livingstone DE, Abernethie AJ, Tsang N, Walker BR, Hadoke PW, Andrew R. Safer topical treatment for inflammation using 5α-tetrahydrocorticosterone in mouse models. Biochem Pharmacol. 2017 Apr 1;129:73-84. doi: 10.1016/j.bcp.2017.01.008. Epub 2017 Jan 24. PMID: 28131845; PMCID: PMC5342892.

[5.] Kodama M, Kodama T, Yoshida M, Ryozo Totania, Aoki K. Hormonal Status of Breast Cancer. II. Abnormal Urinary Steroid Excretion2. Journal of the National Cancer Institute. 1975;54(6):1275-1282. doi:https://doi.org/10.1093/jnci/54.6.1275

[6.] Livingstone DEW, Sooy K, Sykes C, Webster SP, Walker BR, Andrew R. 5α-Tetrahydrocorticosterone: A topical anti-inflammatory glucocorticoid with an improved therapeutic index in a murine model of dermatitis. Br J Pharmacol. 2024 Apr;181(8):1256-1267. doi: 10.1111/bph.16285. Epub 2023 Dec 28. PMID: 37990638.

[8.] Rupa Health. HuMap Sample Report.pdf. Google Docs. Accessed June 14, 2024. https://drive.google.com/file/d/1-d5lSCZ2M1_5YYCfMSqxc6lvUU6fMcaZ/view

[9.] Schiffer L, Barnard L, Baranowski ES, Gilligan LC, Taylor AE, Arlt W, Shackleton CHL, Storbeck KH. Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: A comprehensive review. J Steroid Biochem Mol Biol. 2019 Nov;194:105439. doi: 10.1016/j.jsbmb.2019.105439. Epub 2019 Jul 27. PMID: 31362062; PMCID: PMC6857441.

[10.] Spencer RL, Hutchison KE. Alcohol, aging, and the stress response. Alcohol Res Health. 1999;23(4):272-83. PMID: 10890824; PMCID: PMC6760387.

[11.] Vassiliadi DA, Barber TM, Hughes BA, et al. Increased 5α-Reductase Activity and Adrenocortical Drive in Women with Polycystic Ovary Syndrome. The Journal of Clinical Endocrinology & Metabolism. 2009;94(9):3558-3566. doi:https://doi.org/10.1210/jc.2009-0837

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