Pre-Receptor Regulation of the Androgen Receptor

The conversation discusses the hypothesis that a lack of the enzyme 3-alpha hydroxysteroid dehydrogenase (3α-HSD) on the scalp may contribute to hair loss by allowing DHT to accumulate. Despite interest in this theory, no recent research has been conducted, and current treatments like finasteride and minoxidil remain the most supported options.

The conversation discusses androgen receptor degraders for hair loss, highlighting their potential advantages over traditional AR blockers like RU58841 and pyrilutamide. Concerns about the safety and cost of these treatments are also mentioned.

Androsterone may help with sexual and affective dysfunction from finasteride by replacing disrupted neurosteroids without increasing androgenic side effects. Controlled testing is needed to confirm its effectiveness and safety.

Elevated bile acids can inhibit the enzyme AKR1C2, leading to increased DHT levels, which may accelerate hair loss in those predisposed to androgenetic alopecia. Treatments mentioned include topical minoxidil and finasteride.

Pyrilutamide and RU58841 are androgen receptor antagonists that block receptors without significantly reducing testosterone or DHT levels. Any indirect effect on androgen levels is likely negligible.

Fluridil degrades androgen receptors, which are prevalent in the scalp and other tissues. People with androgenetic alopecia (AGA) may have higher expression of these receptors and 5AR activity in affected scalp areas.