ABSTRACT
BACKGROUND AND OBJECTIVES: Inflammasomes that activate caspase-1 govern the innate immune inflammatory response. Whether hair loss associated with androgenetic alopecia (AGA) involves caspase-1 activation is not known. METHODS: Immunohistochemical staining for caspase-1 was performed on scalp tissue sections, and protein lysates were analyzed from individuals with AGA (no treatment), and individuals with AGA taking finasteride with apparent hair growth, individuals with AGA taking finasteride without noted hair growth, and normal controls. In vitro studies of human keratinocytes were conducted to establish effects of finasteride, dihydrotestosterone (DHT), and testosterone on caspase-1 levels using immunoblot analysis. RESULTS: Caspase-1 is expressed in normal human adult epidermal keratinocytes. Caspase-1 expression is greater in men with AGA. In contrast, in men taking finasteride, caspase-1 levels were lower and were similar to those in normal controls. In vitro studies showed that keratinocytes treated with finasteride in combination with testosterone or DHT resulted in a significant decrease in caspase-1 expression. CONCLUSION: In vivo and in vitro finasteride treatment resulted in lower caspase-1 expression, supporting the idea that androgens influence innate immunity involved in the hair cycle in AGA. These findings may provide a basis for development of novel treatments for inflammatory skin and hair diseases.
Subject(s)
Alopecia/metabolism , Caspase 1/metabolism , Keratinocytes/metabolism , Scalp/metabolism , 5-alpha Reductase Inhibitors/pharmacology , 5-alpha Reductase Inhibitors/therapeutic use , Adult , Aged , Aged, 80 and over , Alopecia/drug therapy , Alopecia/immunology , Androgens/pharmacology , Caspase 1/drug effects , Caspase 1/immunology , Cells, Cultured , Dihydrotestosterone/pharmacology , Finasteride/pharmacology , Finasteride/therapeutic use , Hair/drug effects , Hair/growth & development , Hair/metabolism , Humans , Immunity, Innate , Immunohistochemistry , Inflammasomes , Keratinocytes/drug effects , Male , Middle Aged , Testosterone/pharmacologyABSTRACT
Excessive sebum production is a central aspect of the pathophysiology of acne vulgaris. Sebaceous gland function is under androgen control and it is hypothesized that dihydrotestosterone is formed by the action of 5 alpha-reductase. Type I is the controlling isoenzyme. This study describes a 3-month, multicenter, randomized, placebo-controlled clinical trial with a potent, selective inhibitor of type I 5 alpha-reductase used alone and in combination with systemic minocycline. Inhibition of type I 5 alpha-reductase was not associated with clinical improvement of acne when used alone and did not enhance the clinical benefit of systemic minocycline. These results indicate the need for further work at the molecular level to better understand the action of androgens on sebaceous gland function.
Subject(s)
Acne Vulgaris/drug therapy , Cholestenone 5 alpha-Reductase/antagonists & inhibitors , Double-Blind Method , Drug Therapy, Combination , Humans , Minocycline/administration & dosage , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
BACKGROUND: A number of studies have provided evidence that apoptosis is a central element in the regulation of hair follicle regression. In androgenetic alopecia (AGA), the exact location and control of key players in the apoptotic pathways remains obscure. OBJECTIVE: In the present study, we used a panel of antibodies and investigated the spatial and cellular pattern of expression of caspases and inhibitors of apoptosis (IAPs), such as XIAP and FLIP, in men with normal scalp and in men with AGA before and after 6 months of treatment with 1 mg oral finasteride treatment. METHODS AND RESULTS: Constitutive expression of caspases-1, -3, -8, and -9 and XIAP was detected predominantly within the isthmic and infundibular hair follicle area, basilar layer of the epidermis, and eccrine and sebaceous glands. AGA-affected tissues showed an increase in caspase (-1, -3, -6, -9) immunoreactivity with a concomitant decrease in XIAP staining. After 6 months of finasteride treatment, both caspases and XIAP were similar to levels exhibited by normal subjects. Immunoblot analysis was performed to determine antibody specificity and cellular expression of caspases. Purified populations of keratinocytes, melanocytes, dermal papilla, and dermal fibroblasts derived from human hair follicles were cultured in vitro and treated with 0.5 mm staurosporin. Time-course experiments revealed that processing of caspase-3 is a principal event during apoptosis of these hair cell types. CONCLUSION: These data suggest that alterations in levels of caspases and IAPs regulate hair follicle homeostasis. Moreover, finasteride appears to influence caspase and XIAP expression in hair follicle cells thus signaling anagen, active growth in the hair cycle.
