The uptake and metabolism of radioactively labelled testosterone was investigated in vivo at various time intervals in the skin, plasma and other tissues of adult rats castrated 24 h earlier. After the addition of marker steroids the components of the tissue extracts were separated by partition and development in several chromatographic systems; steroid identification was confirmed by derivative formation and recrystallization to constant ³H:¹⁴C ratio.

The skin resembled the classical androgen target organs in the uptake and retention of both total and unconjugated radioactivity, but the actual composition of the radioactivity present in the skin was markedly different from that in the accessory glands. Little testosterone was recovered from the ventral prostates and 5α-dihydrotestosterone (5α-DHT), often considered the active intracellular androgenic steroid, constantly occupied the largest proportion of the extracted radioactivity. In the skin samples, however, testosterone was always the major unconjugated steroid detected and 4-androstene-3,17-dione, 5α-DHT, 5α-androstane-3α,17β-diol, androsterone and 5α-androstane-3β,17β-diol were only identified in much smaller quantities, even after 5 h. Although the majority of the plasma radioactivity was conjugated or very polar by 20 min, all the steroids found in the skin were present, albeit in different proportions; testosterone was always predominant and 5α-androstane-3β,17β-diol was also detected in larger amounts than the very low levels of the other steroids.

The results suggest that 5α-DHT is not as important in the skin as it is in the prostate of the rat and that other androgenic steroids, most notably testosterone itself, may be involved in the mechanism of androgen action in the skin.

Androgens stimulate many hair follicles to alter hair colour and size via the hair growth cycle; in androgenetic alopecia tiny, pale hairs gradually replace large, pigmented ones. Since stem cell factor (SCF) is important in embryonic melanocyte migration and maintaining adult rodent pigmentation, we investigated SCF/c-Kit signalling in human hair follicles to determine whether this was altered in androgenetic alopecia. Quantitative immunohistochemistry detected three melanocyte-lineage markers and c-Kit in four focus areas: the epidermis, infundibulum, hair bulb (where pigment is formed) and mid-follicle outer root sheath (ORS). Colocalisation confirmed melanocyte c-Kit expression; cultured follicular melanocytes also exhibited c-Kit. Few ORS cells expressed differentiated melanocyte markers or c-Kit, but NKI/beteb antibody, which also recognises early melanocyte-lineage antigens, identified fourfold more cells, confirmed by colocalisation. Occasional similar bulbar cells were seen. Melanocyte distribution, concentration and c-Kit expression were unaltered in balding follicles. Androgenetic alopecia cultured dermal papilla cells secreted less SCF, measured by ELISA, than normal cells. This identifies three types of melanocyte-lineage cells in human follicles. The c-Kit expression by dendritic, pigmenting, bulbar melanocytes and rounded, differentiated, non-pigmenting ORS melanocytes implicate SCF in maintaining pigmentation and migration into regenerating hair bulbs. Less differentiated, c-Kit-independent cells in the mid-follicle ORS stem cell niche and occasionally in the bulb, presumably a local reserve for long scalp hair growth, implicate other factors in activating stem cells. Androgens appear to reduce alopecia hair colour by inhibiting dermal papilla SCF production, impeding bulbar melanocyte pigmentation. These results may facilitate new treatments for hair colour changes in hirsutism, alopecia or greying.