ACTIVITY OF TYPE-1 5-ALPHA-REDUCTASE IS GREATER IN THE FOLLICULAR INFRAINFUNDIBULUM COMPARED WITH THE EPIDERMIS

The enzyme 5 alpha-reductase converts testosterone (T) to dihydrotesto sterone (DHT). Although this enzyme has been localized to various regi ons of the pilosebaceous unit, its activity has not been studied in th e follicular portion of either vellus or sebaceous follicles. The goal of our study was to determine the relative activities of 5 alpha-redu ctase within various regions of these follicles with particular emphas is on the infrainfundibulum. A finding of increased 5 alpha-reductase activity in upper follicles compared to epidermis might support the hy pothesis that increased follicular production of DHT is involved in th e hyperkeratinization observed in this region of the follicle in acne vulgaris, 5 alpha-reductase activity was determined at pH 5 (optimal f or the type 2 isozyme) and pH 7 (optimal for the type 1 isozyme) in is olated infrainfundibular segments from sebaceous and vellus follicles, homogenized epidermis from Various anatomical areas and in microdisse cted segments of the pilosebaceous unit from breast skin of normal sub jects. Enzyme activity was also determined at pH 7 in cultured infrain fundibular keratinocytes and in interfollicular epidermal keratinocyte s. Homogenates of infrainfundibular segments demonstrated significantl y greater activity at pH 7 compared to pH 5 (P < 0.001), confirming ac tivity of the type 1 5 alpha-reductase in this region. Activity of 5 a lpha-reductase was much lower in homogenized epidermis and did not dem onstrate a clear pH preference, Keratinocytes cultured from the infrai nfundibulum demonstrated significantly greater 5 alpha-reductase activ ity compared to keratinocytes from interfollicular epidermis (P = 0.04 ). In the dissected segments of pilosebaceous units from breast skin, 5 alpha-reductase activity was greatest in the sebaceous gland followe d by the sebaceous duct, infrainfundibulum, whole skin and epidermis. These data indicate that 5 alpha-reductase activity varies within regi ons of the pilosebaceous unit and compared with interfollicular epider mal cells, infrainfundibular keratinocytes have an increased capacity for producing androgens which may play a role in the follicular hyperk eratinization seen in acne.