5alpha-dihydrotestosterone (DHT) retards wound closure by inhibiting re-epithelialization

Area of Science:

• Dermatology
• Endocrinology
• Wound Healing Research

Background:

• Elderly males exhibit delayed acute skin wound healing and increased chronic ulceration compared to females.
• Endogenous estrogens enhance, while androgens inhibit, skin repair processes.
• Previous research indicated dihydrotestosterone (DHT) is a potent inhibitor of wound healing, more so than testosterone.

Purpose of the Study:

• To elucidate the central mechanisms by which androgens, specifically DHT, impede skin wound repair.
• To investigate the impact of androgen manipulation on wound re-epithelialization and cellular processes.

Main Methods:

• In vivo studies using rat models with incisional and excisional wounds.
• In vitro assays examining fibroblast-impregnated collagenous discs and epidermal keratinocyte migration.
• Assessment of androgen biosynthesis blockade and beta-catenin expression.

Main Results:

• Blocking dihydrotestosterone (DHT) biosynthesis significantly accelerated re-epithelialization in both incisional and excisional wounds.
• DHT was found to inhibit the in vitro migration of epidermal keratinocytes.
• DHT did not affect the contractile properties of wounds or the migration/proliferation of dermal fibroblasts, indicating a primary effect on re-epithelialization.
• Reduced local beta-catenin expression was observed following DHT biosynthesis blockade.

Conclusions:

• Androgens, particularly DHT, primarily inhibit skin wound repair by impairing keratinocyte re-epithelialization.
• DHT's inhibitory effect on epidermal repair mechanisms, including beta-catenin regulation, contributes to delayed healing in males.
• These findings are significant for understanding and potentially treating chronic ulceration, a condition where male sex is a major risk factor.