DHEA And Frontal Fibrosing Alopecia: Molecular And Physiopathological Mechanisms

[Entropy]

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.

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The importance of the effect of DHEA on mitochondrial oxidative metabolism was stabilished by administration of this hormone in rats. These animals showed increased liver and brain metabolism with elevated brain weight without concurrent increase in body weight.52 The results observed in the topographic response is demonstrative of the variation in distribution of DHEA receptors in the body of these animals.

Tests with radioactive DHEA administered to dogs confirmed their higher metabolism in fibroblasts derived from dermal follicles and, among these, in dermal fibroblasts derived from the follicles of the skulls of the animals, accentuating the topographic differences of their receptors.53

The relation between the activity of DHEA and FFA is also suggested by the reduction of DHEA levels in different conditions characterized by fibrosis, such as occurs in idiopathic pulmonary fibrosis.47 A comparison of the serum levels of DHEA/DHEAS of 137 patients with idiopathic pulmonary fibrosis and 58 controls showed a significant reduction of these hormones in patients, both in plasma and in the bronchoalveolar lavage fluid.


CONCLUSIONS

1. PPARγ is the main regulator of lipid cell metabolism and sebocytes development. The reduction of its activity is responsible for fibrosis;
   
   
2. DHEA is an important stimulator of PPARs;
   
   
3. Reduction of DHEA is observable in some diseases characterized by fibrosis;
   
   
4. Frontal fibrogenic alopecia typically develops in the woman life period in which production of DHEA is decreased;
   
   
5. It is possible that the reduction of the local activity of DHEA is responsible for follicular fibrogenic process of this alopecia;
   
   
6. It is also possible that the better understanding on the variation of topography dynamic of tissue activity of DHEA changes therapeutic strategies in other conditions characterized by fibrosis.

DHEA and frontal fibrosing alopecia: molecular and physiopathological mechanisms

 

[paymanz]

Interesting,thanks!

 

[Gl;itch.e]

BRB rubbing 1,000,000mg DHEA into my scalp!

 

[tca300]

@Gl;itch.e

 

[meatbag]

Meshes well with DRoddy's recent article that is great: The Mysterious Conductor of the Hair Cycle Clock

Some excerpts that are related (emphasis mine);

*"A higher functioning of the adrenal glands and pituitary involve changes in the “stress-response modulators,” the mitochondria.[9] Inhibiting mitochondrial energy production increases the reliance on pituitary and adrenal hormones such as cortisol, prolactin, DHEA, and aldosterone, which are all associated with baldness in both sexes. Moreover, these hormonal changes shift the balance between insulin-like growth factor 1 (IGF-1) and transforming growth factor beta 1 (TGF-b1)—two growth factors that appear to be intimately involved in hair growth as well as provide clues for identifying the missing conductor of the hair cycle clock."

*A deficiency of G6PDH and an excess of aldosterone leads to unmitigated oxidative stress, tissue injury, and an increase in the inflammatory cytokine TGF-b1

*TGF-b1 stimulates the formation of collagen, and overtime this overproduction leads to “perifollicular fibrosis” further reducing the hair follicles’ access to oxygen, sugar, and other nutrients. Levels of TGF-b1 are closely related to the progression of pattern baldness,[23] and alongside hypoxia, the accumulation and activation of mast cells,[24] and an increased concentration of prostaglandins reinforce the view that the defining feature of pattern baldness, a decreased anagen to telogen ratio, is the result of chronic scalp inflammation and an inability to repair.[25] The development of fibrosis in baldness might explain why accidentally setting fire to one's scalp can result in a new head of hair.[26, 27]!!!!

*TGF-b1 appears to share an inverse relationship with the liver's production of IGF-1,[28,29] and in one experiment supplementary IGF-1 stimulated hair follicle development leading the researchers to say that it might be “a promising drug candidate for baldness therapy.”[30] In the 1990s, Keaely et al. demonstrated that IGF-1 inhibits the catagen and telogen phases of the hair growth cycle favoring anagen.[31, 32] More recently, it was discovered that balding hair follicles secreted “significantly less” IGF-1 and “that the downregulation of IGF-1 may be one of the important mechanisms contributing to male pattern baldness.”[33]