Learning Objective

By the end of this section, the learner should be able to:

• Describe the role of 5α-reductase in androgen metabolism.
• Explain the conversion of testosterone to dihydrotestosterone (DHT).
• Identify the key physiologic effects primarily mediated by DHT.
• Recognize the clinical relevance of altered DHT activity.

Overview

5α-reductase is an intracellular enzyme expressed in specific androgen-responsive tissues, including the prostate, external genitalia, skin, and hair follicles. It converts testosterone into dihydrotestosterone (DHT), a more potent androgen that binds the androgen receptor with higher affinity and produces stronger biological effects.

Mechanism

Testosterone diffuses into target cells → 5α-reductase converts it to DHT → androgen receptor is activated → gene transcription is enhanced → amplified androgenic effects.

Activity

Physiologic Effects Primarily Mediated by DHT

• Sexual differentiation – Development of male external genitalia during embryogenesis.
• Prostate growth – Stimulation of prostatic tissue development and maintenance.
• Male-pattern baldness – Androgen-sensitive hair follicle miniaturization.
• Increased sebaceous gland activity – Contributes to acne.
• Nitric oxide (NO) synthase production in penile tissue – Supports erectile function.

Clinical Correlation

Deficiency of 5α-reductase results in impaired conversion of testosterone to DHT, leading to ambiguous or undervirilized external genitalia in genetic males. Excessive DHT activity contributes to benign prostatic hyperplasia and androgenic alopecia.

Activity