Effect of Androgens on Human Fascia

TL;DR

This study shows that male hormones like DHT affect collagen in human fascia, with lower doses (like in females) causing significant changes in collagen types, possibly explaining sex differences in tissue mechanics and pain.

Contribution

The study demonstrates for the first time that androgens modulate collagen production in human fascia in a sex-specific and dose-dependent manner.

Findings

Androgen receptors are present in human fascia from both male and female donors.

Low-dose DHT (0.4 ng/mL) increases collagen I and decreases collagen III in fascial fibroblasts.

Higher DHT doses (4–10 ng/mL) have minimal effects on collagen subtype expression.

Abstract

Sex hormones are known to influence connective tissues, but their effects on fasciae remain poorly understood. Particularly, the influence of male hormones on fasciae has remained poorly understood. This study investigated the presence of androgen receptors in human fascia and the impact of dihydrotestosterone (DHT), the active form of testosterone, on collagen production by fascial fibroblasts. Tissue samples from the thoracolumbar fascia and fascia lata of male and female donors revealed androgen receptor expression in both sexes. When treated with different concentrations of DHT corresponding to female and male physiological levels, fibroblasts responded in a dose-dependent manner. At the lower, female-level concentration (0.4 ng/mL), collagen type I significantly increased (from ~2% to 4.8% of the cell area), whereas collagen type III decreased markedly (from ~10.4% to 3.3%), suggesting a shift toward a more fibrotic extracellular matrix. In contrast, higher, male-level concentrations (4–10 ng/mL) induced minimal or no significant changes. These findings indicate that androgens can modulate fascia structure and may help explain greater hormone sensitivity observed in females, whose collagen balance is more responsive to hormonal fluctuations. This has relevant implications for understanding sex differences in tissue mechanics, injury risk, and recovery, and may inform personalized approaches in rehabilitation, sports medicine, and connective tissue disorder management.

Androgens are emerging as important regulators of connective tissue remodeling, but current knowledge about their role in human fascia is still limited. This study examined the expression of the androgen receptor (AR) in human deep fascia and investigated the effects of dihydrotestosterone (DHT) on collagen production by fascial fibroblasts. Fascia lata and thoracolumbar fascia samples were collected from four adult donors (two male and two female). AR expression was assessed by immunohistochemistry and immunocytochemistry. Fascial fibroblasts were treated in vitro for 24 h with DHT at concentrations reflecting physiological levels: 0.4 ng/mL (female), 4 ng/mL (male average), and 10 ng/mL (high male dose). Collagen content was quantified using Picrosirius Red staining, and collagen I and III were evaluated using immunocytochemistry and image analysis, and were compared to an untreated control group. AR was detected in all samples. Low-dose DHT (0.4 ng/mL) significantly increased collagen I (4.80 ± 1.75%) and decreased collagen III (3.32 ± 0.46%) compared to controls (2.09 ± 0.91% and 10.46 ± 0.53%, respectively; p < 0.05). Higher DHT doses induced smaller or no significant changes in collagen subtype expression (e.g., 10 ng/mL: 2.03 ± 0.81% for collagen I, 8.49 ± 1.85% for collagen III). The results demonstrated that human fascia is hormonally responsive via AR, with DHT modulating matrix composition in a dose-dependent manner. The distinct effects at male and female levels may help explain gender differences in fascial stiffness and pain.

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