SRD5A2 Variants ∞ Area

SRD5A2 Variants

Meaning

SRD5A2 variants are genetic alterations within the steroid 5-alpha reductase type 2 gene, which encodes an enzyme converting testosterone into dihydrotestosterone (DHT). These changes can alter enzyme function, affecting DHT production or action.

Context

The SRD5A2 enzyme functions within the endocrine system, specifically in androgen-responsive tissues like the prostate, hair follicles, and external genitalia. Its action is a critical step in peripheral steroid hormone metabolism, influencing local DHT concentrations vital for male sexual development and prostate health.

Significance

SRD5A2 variants hold clinical significance due to their impact on androgen-dependent processes. Specific variants associate with 5-alpha reductase deficiency, a 46,XY disorders of sex development causing varied undervirilization. These genetic changes also influence susceptibility to benign prostatic hyperplasia, modulate prostate cancer risk, and affect androgenetic alopecia, impacting personalized patient care.

Mechanism

At a molecular level, the SRD5A2 enzyme catalyzes testosterone’s conversion to dihydrotestosterone by reducing the delta-4,5 double bond of the steroid A-ring. Genetic variants can alter the enzyme’s structure, affecting its catalytic efficiency, substrate binding, or stability. Such alterations lead to diminished or, rarely, enhanced DHT production, directly modulating androgen receptor activation in target tissues.

Application

Clinical application of SRD5A2 variant understanding involves diagnostic genetic testing for individuals with ambiguous genitalia or other features of 5-alpha reductase deficiency. Knowledge of these variants informs personalized risk assessment for benign prostatic hyperplasia and prostate cancer. It also aids in predicting responses to 5-alpha reductase inhibitor medications like finasteride or dutasteride. This information assists clinicians in tailoring treatment and providing genetic counseling.

Metric

The impact of SRD5A2 variants is assessed via biochemical and genetic metrics. Serum testosterone and dihydrotestosterone concentrations, especially the T/DHT ratio, indicate 5-alpha reductase activity. Genetic sequencing identifies specific variants for diagnosis or predisposition. Clinical evaluation of virilization status provides important phenotypic data.

Risk

Mismanagement or misinterpretation of SRD5A2 variants carries risks, including delayed or incorrect diagnosis for individuals with disorders of sex development, leading to psychological distress and inappropriate interventions. For patients on 5-alpha reductase inhibitors, genetic variation may influence treatment efficacy and side effects like sexual dysfunction or mood changes. Genetic counseling is essential to mitigate these risks, ensuring accurate understanding and informed decision-making.

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How Do Genetic Variations Affect Testosterone Therapy Dosing?

Genetic variations alter testosterone metabolism, receptor sensitivity, and binding protein levels, necessitating personalized dosing for optimal therapeutic outcomes.

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HRTioJuly 22, 2025