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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