EFFECT OF ORAL ISOTRETINOIN TREATMENT ON SKIN ANDROGEN RECEPTOR LEVELS IN MALE ACNEIC PATIENTS

An oral daily dose (mean +/- SD, 0.75 +/- 0.05 mg/kg) of isotretinoin was administered for 3 months to six male patients with acne (scores o f 4 and 5 according to Rosenfield). The therapy resulted in complete r esolution of acne in four patients and improved acne significantly (sc ore 1) in two patients. In accordance with recent findings, no change in serum testosterone and significant decreases in 5 alpha-dihydrotest osterone, 5 alpha-androstane-3 alpha,17 beta-diol glucosiduronate, and androsterone glucosiduronate levels were observed after treatment. An drogen receptor status was investigated in back skin biopsies obtained in acne areas before and after 3 months of isotretinoin treatment. Th e treatment did not modify the binding affinity constant of skin andro gen receptor (0.44 vs. 0.32 nmol/L), but it did induce a 2.6-fold decr ease in its binding capacity constant (62 vs. 24 fmol/mg cytosolic pro tein), as assessed by Scatchard plot and confirmed immunologically by Western blot analysis. These data clearly showed that skin androgen re ceptor was sensitive to oral isotretinoin administration in acneic pat ients. The decrease in skin androgen receptor levels (this study) and the recently reported suppression of skin 5 alpha-dihydrotestosterone production by isotretinoin treatment appeared consistent with the invo lvement of androgen receptor and 5 alpha-dihydrotestosterone in the pa thogenesis of acne. Indeed, sebum production is under androgen control , and an abnormal response of the pilosebaceous unit to androgens appe ars to be implicated in the pathogenesis of acne. These observations w ere consistent with the absence of sebum in complete androgen-insensit ive patients and normal sebum production in male pseudohermaphrodites.