Posts Tagged ‘Androgen Receptor’

Evidence of increased DNA methylation of the androgen receptor gene in occipital hair follicles from men with androgenetic alopecia

Monday, May 9th, 2011

Br J Dermatol. 2011 Mar 24. doi: 10.1111/j.1365-2133.2011.10335.x. [Epub ahead of print]

Evidence of increased DNA methylation of the androgen receptor gene in occipital hair follicles from men with androgenetic alopecia.

Cobb JE, Wong NC, Yip LW, Martinick J, Bosnich R, Sinclair RD, Craig JM, Saffery R, Harrap SB, Ellis JA.

Department of Physiology, University of Melbourne, Victoria Australia 3010 Developmental Epigenetics, Murdoch Childrens Research Institute, Flemington Road, Parkville, Victoria Australia 3052 Department of Dermatology, St Vincent’s Hospital, Victoria Australia 3065 New Hair Clinic, 627 Chapel Street, South Yarra, Victoria Australia 3141 National Hair Institute, 104 Canterbury Road, Middle Park, Victoria Australia 3206 Environmental and Genetic Epidemiology

In order to compare and clarify the underlying hormonal basis, a study was conducted in 12 young women (ages 14-33) and 12 young men (ages 18-30) with AGA (Sawaya and Price, 1997). Androgen receptor, type I and type II 5x-reductase, and cytochrome p-450 aromatase, were measured in hair follicles from scalp biopsies of these young subjects. Both young women and young men had higher levels of type I and type II 5x-reductase and androgen receptors in frontal hair follicles compared to occipital hair follicles; however, the levels in women were approximately half the levels in men (Sawaya and Price, 1997). At the same time, young women had much higher levels of cytochrome p-450 aromatase in frontal follicles than men who had minimal aromatase, and women had even higher aromatase levels in occipital follicles. The differences in aromatase, which is capable of converting testosterone to estradiol, are particularly notable. The findings of this study suggest that the milder expression of AGA in women may in part be the result of lower levels of 5x-reductase and androgen receptors in frontal follicles of women compared to levels in men; additionally, higher levels of aromatase in women may result in increased local formation of estradiol from testosterone, and less formation of 5x-reductase products such as DHT.

Dermal Papilla Androgen Sensitivity, Androgen Receptors & Methylation

Thursday, December 30th, 2010

Due to the understanding of male pattern baldness as Androgenic Alopecia (i.e. as an androgen-dependent process), many studies have focused on androgen metabolism (AM) in the body and how androgens effect hair.  Studies have shown that “all dermal papilla cells from androgen-sensitive sites contain low capacity, high affinity androgen receptors.” [18]

The dermal papilla (DP), at the base of the hair follicle, has androgen receptors (AR’s) that androgens from the blood bind to. In androgen-sensitive follicles, the androgens are synthesized and diffused over small distances; this induces changes in neighboring cells (like keratinocytes cells) in what is known as “paracrine interactions”. The diffusible proteins are called paracrine factors. [18]

When beard and scalp cells were incubated in androgens, androgens stimulated the cells’ ability to triggered mitosis (cell division) in beard cells but not in scalp cells. The interesting outcome here was that incubation with androgens had the exact opposite effect on scalp cells; these (scalp) cells’ mitogenic capacity was inhibited. [18]

Androgen-sensitive follicles are not simply targeted and affected by androgens; they are actually involved in androgen metabolism (AM) and can convert androgens using steroid-producing (steroidogenic) enzymes, also known as intrafollicular steroidogenic enzymes. [25]

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A 2004 study shed more light on specific processes that shorten the hair cycle (that occur within the DP). According to the study, the three processes are as follows: “(1) the conversion of testosterone to DHT by type II 5-alpha-reductase; (2) the synthesis of TGF-beta2 in dermal papilla cells; and (3) the activation of the intrinsic caspase network.” [6]

The research seems to indicate AM activity at the DP of the hair follicle, amongst other interactions is not fully understood yet. Some of the known intrafollicular steroidogenic enzymes found in the DP are: Steroid Sulfatase (STS), 17beta-hydroxysteroid dehydrogenases (17b-HSD), 3beta-hydroxysteroid dehydrogenases (3b-HSD)  and type 1 and 2 5alpha-reductase (type 1 and type 2 5alpha-R). Type 2 5-alpha-reductase has been the target of a number of studies that showed it to accelerate the conversion of free testosterone into DHT. [10] [11] [12] [24] [25] [28] [31]

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