DHEA and frontal fibrosing alopecia: molecular and physiopathological mechanisms

Abstract The transforming growth factor-beta 1 (TGFβ1) promotes fibrosis, differentiating epithelial cells and quiescent fibroblasts into myofibroblasts and increasing expression of extracellular matrix. Recent investigations have shown that PPAR (peroxisome proliferator-activated receptor*) is a negative regulator of fibrotic events induced by TGFβ1. Dehydroepiandrosterone (DHEA) is an immunomodulatory hormone essential for PPAR functions, and is reduced in some processes characterized by fibrosis. Although scarring alopecia characteristically develops in the female biological period in which occurs decreased production of DHEA, there are no data in the literature relating its reduction to fibrogenic process of this condition. This article aims to review the fibrogenic activity of TGFβ1, its control by PPAR and its relation with DHEA in the frontal fibrosing alopecia.

DHEA(S): the fountain of youth.

Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) are weak androgens produced primarily by the adrenal gland. Although their plasma concentrations by far exceed those of any other adrenal product, their physiological roles have not yet been determined. In plasma, where the major portion of these hormones is present in the sulfate form, it is possible that DHEAS serves as a reservoir for DHEA. Since various tissues have been shown to contain steroid sulfatases. The peak plasma levels of DHEA and DHEAS occur at approximately age 25 years, decrease progressively thereafter, and diminish by 95 per cent around the age of 85 years. The decline of DHEAS concentrations with aging has led to the suggestion that DHEAS could play a role in itself and be implicated in longevity. Moreover, the epidemiological evidence has shown that adult men with high plasma DHEAS levels are less likely to die of cardiovascular disease. DHEA has also been shown to increase the body's ability to transform food into energy and burn off excess fat. Another recent finding involves the anti-inflammatory properties of DHEA. It has been known that DHEA can lower the levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha). It should be pointed out that chronic inflammation is known to play a critical role in the development of the killer diseases of aging: heart disease, Alzheimer's disease and certain types of cancer. In conclusion, DHEA or DHEAS administration combined with conventional treatment may be implicated in particular conditions to improve the quality of life.