mTORC1 activity negatively regulates human hair follicle growth and pigmentation.

Dysregulation of the activity of the mechanistic target of rapamycin complex 1 (mTORC1) is commonly linked to aging, cancer, and genetic disorders such as tuberous sclerosis (TS), a rare neurodevelopmental multisystemic disease characterized by benign tumors, seizures, and intellectual disability. Although patches of white hair on the scalp (poliosis) are considered as early signs of TS, the underlying molecular mechanisms and potential involvement of mTORC1 in hair depigmentation remain unclear. Here, we have used healthy, organ-cultured human scalp hair follicles (HFs) to interrogate the role of mTORC1 in a prototypic human (mini-)organ. Gray/white HFs exhibit high mTORC1 activity, while mTORC1 inhibition by rapamycin stimulated HF growth and pigmentation, even in gray/white HFs that still contained some surviving melanocytes. Mechanistically, this occurred via increased intrafollicular production of the melanotropic hormone, α-MSH. In contrast, knockdown of intrafollicular TSC2, a negative regulator of mTORC1, significantly reduced HF pigmentation. Our findings introduce mTORC1 activity as an important negative regulator of human HF growth and pigmentation and suggest that pharmacological mTORC1 inhibition could become a novel strategy in the management of hair loss and depigmentation disorders.

Caspase-1 level is higher in the scalp in androgenetic alopecia.

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.

The current role of laser/light sources in the treatment of male and female pattern hair loss.

Over the past several years there has been great interest in the potential role of laser/light-based treatments for male and female pattern hair loss. Despite aggressive marketing and centers claiming great success in the treatment of hair loss there is little scientific data supporting laser/light sources in hair loss. This paper is a consensus of hair loss experts on the current scientific data, mechanisms of action, safety, protocols and recommendations regarding laser/light treatment for hair loss. The authors believe that, while seemingly safe, there are no controlled, peer-reviewed studies validating current devices for hair loss and that all patients should be medically evaluated for any hair loss by a physician specialist to rule out other underlying medical conditions or the etiology of hair loss.