Posts Tagged ‘Androgen Metabolism’

British Journal of Dermatology – April 2006 – “Inhibitory autocrine factors produced by the mesenchyme-derived hair follicle dermal papilla may be a key to male pattern baldness”

Tuesday, May 24th, 2011

Archived study

British Journal of Dermatology – Volume 154, Issue 4, pages 609–618, April 2006

Inhibitory autocrine factors produced by the mesenchyme-derived hair follicle dermal papilla may be a key to male pattern baldness

1. K. Hamada1,2,3,
2. V.A. Randall1

Article first published online: 20 FEB 2006

DOI: 10.1111/j.1365-2133.2006.07144.x

Summary

Background Androgenetic alopecia, or male pattern baldness, is a common, progressive disorder where large, terminal scalp hairs are gradually replaced by smaller hairs in precise patterns until only tiny vellus hairs remain. This balding can cause a marked reduction in the quality of life. Although these changes are driven by androgens, most molecular mechanisms are unknown, limiting available treatments. The mesenchyme-derived dermal papilla at the base of the mainly epithelial hair follicle controls the type of hair produced and is probably the site through which androgens act on follicle cells by altering the regulatory paracrine factors produced by dermal papilla cells. During changes in hair size the relationship between the hair and dermal papilla size remains constant, with alterations in both dermal papilla volume and cell number. This suggests that alterations within the dermal papilla itself play a key role in altering hair size in response to androgens. Cultured dermal papilla cells offer a useful model system to investigate this as they promote new hair growth in vivo, retain characteristics in vitro which reflect their parent follicle’s response to androgens in vivo and secrete mitogenic factors for dermal papilla cells and keratinocytes.

Objectives To investigate whether cultured dermal papilla cells from balding follicles secrete altered amounts/types of mitogenic factors for dermal papilla cells than those from larger, normal follicles. We also aimed to determine whether rodent cells would recognize mitogenic signals from human cells in vitro and whether factors produced by balding dermal papilla cells could alter the start of a new mouse hair cycle in vivo.

Methods Dermal papilla cells were cultured from normal, balding and almost clinically normal areas of balding scalps and their ability to produce mitogenic factors compared using both human and rat whisker dermal papilla cells as in vitro targets and mouse hair growth in vivo.

Results Normal scalp cells produced soluble factors which stimulated the growth of both human scalp and rat whisker dermal papilla cells in vitro, demonstrating dose-responsive mitogenic capability across species. Although balding cells stimulated some growth, this was much reduced and they also secreted inhibitory factor(s). Balding cell media also delayed new hair growth when injected into mice.

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The Patterned Baldness Non Androgen-Dependent Model

Monday, January 3rd, 2011

More recently, on May of 2010, a study published by the Royal Hallamshire Hospital in the UK titled “Female pattern hair loss in complete androgen insensitivity syndrome” showed a puzzling finding, namely that women with complete insensitivity to androgens still exhibited AGA.

This is stated clearly in this quote: “We describe female pattern hair loss occurring in a patient with complete androgen insensitivity syndrome suggesting that mechanisms other than direct androgen action contribute to this common form of hair loss in women”. [30]

This study shows that other factors besides androgens and androgen metabolism maybe at play here.

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The above was written on July 23, 2010

The Genetic Link

Thursday, December 30th, 2010

Looking at research into Androgenic Alopecia (AGA) here’s what I found:

Hair follicles in different parts of the human body behave differently throughout the human lifespan. Beard growth is androgen-dependent, while hair sensitive to androgen experiences thinning as result of androgens. [25]

It seems androgens cause beard hair, armpit (axillary) hair and pubic hair follicles to enlarge while frontal and vertex scalp hair decrease is size. Others hair follicles like eyebrows and eyelashes don’t seem to change in size. [28]

Researchers in one study concluded this opposite impact of androgens on hair follicles of the beard and scalp was due “to differential gene expression within hair follicles”. [18] Another study stated the factors behind AGA “to be genetic predisposition coupled with the presence of sufficient circulating androgens” and “require the inheritance of several genes”. [3]

A study published in 2005 summarized the role of genetics with AGA by saying AGA is “androgen dependent, and genetic predisposition is the major requirement for the phenotype.”[9-] In other words, we can define AGA not only as androgen-dependent but also as a genetic condition.

Androgens would have no effect if it wasn’t for androgen receptors (AR’s). AR’s are what enables the human body to respond to androgens, and thus play a crucial role in male sexual development. Genetic variations in the AR gene are more common in men with an early onset of AGA.

German researchers named the androgen receptor gene as the cardinal prerequisite for balding.[9-] They concluded a certain variant of the androgen receptor is needed for AGA to develop. In the same year the results of this study were confirmed by other researchers.[10-]

This gene is recessive and a female would need two X chromosomes with the defect to show typical male pattern alopecia. Seeing that androgens and their interaction with the androgen receptor are the cause of AGA it seems logical that the androgen receptor gene plays an important part in its development.

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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]

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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