What is the relationship between the Androgen Receptor (AR) gene and the development of Androgenetic Alopecia (male pattern baldness), and how does testosterone play a role in this process?

From the Guidelines

The Androgen Receptor (AR) gene plays a crucial role in the development of Androgenetic Alopecia (male pattern baldness) by making hair follicles more sensitive to dihydrotestosterone (DHT), a potent form of testosterone. The relationship between the AR gene and the development of Androgenetic Alopecia is complex, involving the conversion of testosterone to DHT by the enzyme 5-alpha reductase, which then binds to androgen receptors in hair follicles, leading to follicle shrinkage and hair loss in genetically susceptible men 1. Here's how it works:

• The AR gene produces androgen receptors in hair follicles.
• Testosterone is converted to DHT by an enzyme called 5-alpha reductase.
• DHT binds to androgen receptors in hair follicles.
• In men with certain AR gene variants, this binding causes follicles to shrink over time, leading to baldness. To combat this process, two main treatments are commonly used:
• Finasteride (1mg daily oral tablet): Blocks the conversion of testosterone to DHT, as shown in studies where finasteride lowered PSA levels by 50% after 12 months of therapy 1.
• Minoxidil (5% solution applied to scalp twice daily): Promotes hair growth through other mechanisms. These treatments are most effective when started early and used consistently, and can slow or stop hair loss and sometimes regrow hair, but results vary, and side effects are possible, so consult a doctor before starting treatment 1. Understanding this genetic and hormonal interplay explains why male pattern baldness runs in families and why it's more common in men than women, who have lower levels of androgens. The use of 5-alpha reductase inhibitors, such as finasteride, is a well-established treatment for Androgenetic Alopecia, and can be effective in reducing hair loss and promoting hair growth.

From the Research

Relationship between Androgen Receptor (AR) gene and Androgenetic Alopecia

• The Androgen Receptor (AR) gene plays a significant role in the development of Androgenetic Alopecia (male pattern baldness) 2, 3, 4, 5, 6.
• Research suggests that the interaction between androgen-bound AR and beta-catenin can inhibit Wnt signaling, leading to hair loss 2.
• Studies have shown that transgenic mice overexpressing human AR in the skin exhibit delayed hair regeneration, mimicking the AGA scalp, when exposed to high levels of 5alpha-dihydrotestosterone 2.

Role of Testosterone in Androgenetic Alopecia

• Testosterone, specifically dihydrotestosterone (DHT), is a key player in the development of Androgenetic Alopecia 3, 4.
• DHT is converted from testosterone by the enzyme 5-alpha-reductase and binds to the androgen receptor, leading to hair miniaturization and loss 3, 4.
• The AR antagonist bicalutamide has been shown to partly reverse the effects of DHT on hair growth, suggesting that AR plays a crucial role in androgen-mediated hair loss 4.

Genetic Predisposition to Androgenetic Alopecia

• Androgenetic Alopecia is a complex condition with a strong heritable component, and genetic factors contribute to the development of the disease 5, 6.
• The AR polyglycine repeat polymorphism has been investigated as a potential susceptibility factor, but studies have found no significant association between this polymorphism and Androgenetic Alopecia 5.
• Other genetic variants, including those in the non-coding region of the AR gene, may contribute to the development of Androgenetic Alopecia, but further research is needed to identify these variants 5, 6.