docj077
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...that I felt everyone should be aware of. Not because it's some giant breakthrough, but because it's good review for the veteran posters and a good source of information of the new guys that want to know a little bit about how the skin and hair works. This article is lacking a few newer discoveries, but it's good nonetheless.
http://edrv.endojournals.org/cgi/content/full/21/5/457
A couple of areas interested me. Mostly because they seem to be topics that are talked about on here a lot and many people think that they are new discoveries when the research has been around for nearly fifteen years. Plus, some people like to argue about where "such and such" receptor or enzyme is located or not located. This will help everyone out a bit.
"N. Androgen and estrogen receptors
Sex steroid receptors belong to the superfamily of trans-acting transcriptional factors, similar to glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) (36, 68). They are widely distributed in all skin compartments, and their density and expression level vary depending on anatomic site and gender (3, 4, 12, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173). The well recognized androgen effects on hair growth and sebaceous gland functions are related to expression of the corresponding androgen receptors (ARs) in epithelial cells of those adnexal structures and in specialized dermal papilla fibroblasts that regulate hair morphogenesis (161, 162, 163, 164, 165). ARs are also expressed in other adnexal structures, in epidermal keratinocytes and melanocytes, dermal fibroblasts, and resident and circulating cells of the skin immune system (3, 4, 12, 31, 160, 161, 162, 163, 164, 165, 169). Similar to ARs, estrogen receptors (ERs) are also expressed in the epidermal, adnexal, and dermal compartments of the skin (3, 4, 12, 166, 167, 168, 170, 171, 172, 173). ERs have been detected variably, depending on the sensitivity method and presence or absence of pathology, in epithelial cells of epidermis, hair follicle, sebaceous, eccrine and apocrine glands, in melanocytes, and in dermal fibroblasts. Thus, both estrogens and androgens regulate hair growth, sebaceous gland function, proliferation and differentiation of epithelial cells of the epidermis and adnexa, functional activity of dermal fibroblasts and fibrocytes, wound healing, and skin immune cells activity. There are also data showing that androgens and estrogens can modulate proliferation and melanogenesis in cultured melanocytes (169, 170, 171). Lastly, transgenic male mice overexpressing GH show overgrowth of the skin that is androgen dependent, e.g., it is not observed in females or in castrated males (97).
Clinical signs of androgen excess include acne, hirsutism, and androgenic alopecia (3, 36, 37, 163, 164). Acne results from follicular hyperkeratinization, increased sebum production, and from the release of lipases and proinflammatory mediators by Propionicum acnes. In these conditions, androgens [mainly dihydrotestosterone (DHT) and to a lesser degree testosterone] mediate the increased sebum production and follicular hyperkeratinization (3, 37, 163, 164). Hirsutism and androgenic alopecia are associated with increased production of DHT within the dermal papilla of androgen-responsive hair follicles of the face, chest, genital skin, and scalp (3, 12, 31, 37, 163). Conversely, in males with androgen deficiency, the skin remains thin and fine; sebaceous and apocrine glands and sexual hair follicles remain dormant; beard, axillary, and pubic hair do not develop and neither does androgenic alopecia; and there is also a general decrease in skin pigmentation (3, 37, 163). Increased estrogen levels, for example during pregnancy, can lead to hyperpigmentation of nipples, areolae, genital skin, and facial skin (3). The latter, known as melasma, is exacerbated by sun exposure (3). In addition, preexisting nevi and ephelides darken, and telangiectasia, spider angioma, and palmar erythema may develop (3, 37). "
"F. Sex steroid hormones
The skin can transform the steroids dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) into active androgens and estrogens (4, 160, 286, 287, 288). Specifically, enzymatic activity corresponding to 3ß-hydroxysteroid dehydrogenase/5–4 isomerase (3ß-HSD) has been localized to the sebaceous glands and, to a lesser degree, in hair follicles, epidermis, and eccrine glands, while 17ß-hydroxysteroid dehydrogenase (17ß-HSD) has been localized to follicular and epidermal keratinocytes (287, 288, 289, 290, 291). 3ß-HSD converts DHEA into 4-androstenedione, and 5-androstene-3ß,17ß-diol into testosterone, while 17ß-HSD converts DHEA into 5-androstene-3ß,17ß-diol, 4-androstenedione into testosterone, and androstanedione into DHT (4, 36, 160). Testosterone is also converted into DHT through the action of a 5-reductase, detected in dermal and dermal papilla fibroblasts, follicular and epidermal keratinocytes, and sebaceous and apocrine glands (4, 160, 164, 286, 289, 290, 291, 292, 293, 294, 295, 296, 297). There are two isozymic forms of the 5-reductase, but the skin expresses predominantly the type I in a highly specific cellular and regional distribution (290, 291, 292, 293, 294, 295, 296). Nevertheless, cutaneous expression of 5-reductase type 2 has been also reported, but at much lower levels; this form has been immunodetected in hair follicles of human scalp (295, 296). The skin immune system can also convert DHEA into 5-androstene-3ß,17ß-diol and into 5-androstene-3ß,7ß,17ß-triol. Cutaneous conversion of testosterone into estradiol is mediated by an aromatase expressed in dermal fibroblasts and adipocytes, but not in keratinocytes (4). However, in keratinocytes 17ß-HSD can transform 17ß-estradiol into estrone or estrone into 17ßestradiol (286)."
The stuff about hyperkeratinization secondary to androgen exposure sort of reminded me of a lot of the IGF-1 stuff that has been posted around here lately. I've also been looking at some studies that demonstrate that increased IGF-1 causes hyperkeratinization and as we all remember one of the supposed growth factors for hair is IGF-1. So, it's not to difficult to conclude that increased androgen receptor function or increased androgens in the scalp will cause hyperkeratinization and a lack of keratinocyte differentiation. Essentially, preventing hair growth. What is interesting is that the article points out that men with androgen deficiency have thinner skin, lack the hyperkeratinization, and have no hair loss.
This article also points out that there are androgen receptors on the dermal fibroblasts, keratinocytes, and melanocytes. The last one interested me as some people complain of greying hair with dutasteride or finasteride. A lack of potent androgens through 5AR inhibition could definitely cause decreased melanocyte function and decreased pigment production.
I just wanted to throw some of this stuff out there as I'm kind of doing some research in my spare time. My next step is to look for a link between male pattern baldness and psoriasis. Afterall, both processes seem to involve hyperkeratinization and it would not surprise me if the underlying cause of psoriasis ends up being somehow linked with androgens.
I'm sure that everyone who is interested already knows about the perifollicular fibrosis and keratinocyte death associated with increased TGF-beta in male pattern baldness patients.
Personally, I think the TGF-beta mechanism is merely the body's way of trying to protect itself from this hyperkeratinization, lack of keratinocyte differentiation, and increased keratinocyte proliferation secondary to increased production of pro-growth IGF-1 due to increased androgen receptor sensitivity in male pattern baldness patients. Unfortunately, the increased TGF-beta also leads to keratinocyte death, decreased collagenase, increased collagen deposition, and a reduction in hair growth. Increased IGF-1 also leads to an increase in the local immune response.
With what I have written down, I can explain how minoxidil, 5AR inhibitors, apple poly, immune suppressants, and nizoral all work. I can also explain why drugs like accutane are the enemy. Lastly, I think that i can explain why male pattern baldness happens on the scalp and not on the rest of the body. The last one might be pushing it, but I might have a pretty good idea.
For everyone else, I'm truly looking for opinions on all this stuff. Don't be shy. There are a lot of good studies that are cited. Use them to further your knowledge base and maybe we can actually find a good treatment instead of dwelling on theories and studies that have been posted more that 5-15 years ago.
If this is supposed to be in the experimental section, would a moderator please move it there. Thank you.
http://edrv.endojournals.org/cgi/content/full/21/5/457
A couple of areas interested me. Mostly because they seem to be topics that are talked about on here a lot and many people think that they are new discoveries when the research has been around for nearly fifteen years. Plus, some people like to argue about where "such and such" receptor or enzyme is located or not located. This will help everyone out a bit.
"N. Androgen and estrogen receptors
Sex steroid receptors belong to the superfamily of trans-acting transcriptional factors, similar to glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) (36, 68). They are widely distributed in all skin compartments, and their density and expression level vary depending on anatomic site and gender (3, 4, 12, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173). The well recognized androgen effects on hair growth and sebaceous gland functions are related to expression of the corresponding androgen receptors (ARs) in epithelial cells of those adnexal structures and in specialized dermal papilla fibroblasts that regulate hair morphogenesis (161, 162, 163, 164, 165). ARs are also expressed in other adnexal structures, in epidermal keratinocytes and melanocytes, dermal fibroblasts, and resident and circulating cells of the skin immune system (3, 4, 12, 31, 160, 161, 162, 163, 164, 165, 169). Similar to ARs, estrogen receptors (ERs) are also expressed in the epidermal, adnexal, and dermal compartments of the skin (3, 4, 12, 166, 167, 168, 170, 171, 172, 173). ERs have been detected variably, depending on the sensitivity method and presence or absence of pathology, in epithelial cells of epidermis, hair follicle, sebaceous, eccrine and apocrine glands, in melanocytes, and in dermal fibroblasts. Thus, both estrogens and androgens regulate hair growth, sebaceous gland function, proliferation and differentiation of epithelial cells of the epidermis and adnexa, functional activity of dermal fibroblasts and fibrocytes, wound healing, and skin immune cells activity. There are also data showing that androgens and estrogens can modulate proliferation and melanogenesis in cultured melanocytes (169, 170, 171). Lastly, transgenic male mice overexpressing GH show overgrowth of the skin that is androgen dependent, e.g., it is not observed in females or in castrated males (97).
Clinical signs of androgen excess include acne, hirsutism, and androgenic alopecia (3, 36, 37, 163, 164). Acne results from follicular hyperkeratinization, increased sebum production, and from the release of lipases and proinflammatory mediators by Propionicum acnes. In these conditions, androgens [mainly dihydrotestosterone (DHT) and to a lesser degree testosterone] mediate the increased sebum production and follicular hyperkeratinization (3, 37, 163, 164). Hirsutism and androgenic alopecia are associated with increased production of DHT within the dermal papilla of androgen-responsive hair follicles of the face, chest, genital skin, and scalp (3, 12, 31, 37, 163). Conversely, in males with androgen deficiency, the skin remains thin and fine; sebaceous and apocrine glands and sexual hair follicles remain dormant; beard, axillary, and pubic hair do not develop and neither does androgenic alopecia; and there is also a general decrease in skin pigmentation (3, 37, 163). Increased estrogen levels, for example during pregnancy, can lead to hyperpigmentation of nipples, areolae, genital skin, and facial skin (3). The latter, known as melasma, is exacerbated by sun exposure (3). In addition, preexisting nevi and ephelides darken, and telangiectasia, spider angioma, and palmar erythema may develop (3, 37). "
"F. Sex steroid hormones
The skin can transform the steroids dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) into active androgens and estrogens (4, 160, 286, 287, 288). Specifically, enzymatic activity corresponding to 3ß-hydroxysteroid dehydrogenase/5–4 isomerase (3ß-HSD) has been localized to the sebaceous glands and, to a lesser degree, in hair follicles, epidermis, and eccrine glands, while 17ß-hydroxysteroid dehydrogenase (17ß-HSD) has been localized to follicular and epidermal keratinocytes (287, 288, 289, 290, 291). 3ß-HSD converts DHEA into 4-androstenedione, and 5-androstene-3ß,17ß-diol into testosterone, while 17ß-HSD converts DHEA into 5-androstene-3ß,17ß-diol, 4-androstenedione into testosterone, and androstanedione into DHT (4, 36, 160). Testosterone is also converted into DHT through the action of a 5-reductase, detected in dermal and dermal papilla fibroblasts, follicular and epidermal keratinocytes, and sebaceous and apocrine glands (4, 160, 164, 286, 289, 290, 291, 292, 293, 294, 295, 296, 297). There are two isozymic forms of the 5-reductase, but the skin expresses predominantly the type I in a highly specific cellular and regional distribution (290, 291, 292, 293, 294, 295, 296). Nevertheless, cutaneous expression of 5-reductase type 2 has been also reported, but at much lower levels; this form has been immunodetected in hair follicles of human scalp (295, 296). The skin immune system can also convert DHEA into 5-androstene-3ß,17ß-diol and into 5-androstene-3ß,7ß,17ß-triol. Cutaneous conversion of testosterone into estradiol is mediated by an aromatase expressed in dermal fibroblasts and adipocytes, but not in keratinocytes (4). However, in keratinocytes 17ß-HSD can transform 17ß-estradiol into estrone or estrone into 17ßestradiol (286)."
The stuff about hyperkeratinization secondary to androgen exposure sort of reminded me of a lot of the IGF-1 stuff that has been posted around here lately. I've also been looking at some studies that demonstrate that increased IGF-1 causes hyperkeratinization and as we all remember one of the supposed growth factors for hair is IGF-1. So, it's not to difficult to conclude that increased androgen receptor function or increased androgens in the scalp will cause hyperkeratinization and a lack of keratinocyte differentiation. Essentially, preventing hair growth. What is interesting is that the article points out that men with androgen deficiency have thinner skin, lack the hyperkeratinization, and have no hair loss.
This article also points out that there are androgen receptors on the dermal fibroblasts, keratinocytes, and melanocytes. The last one interested me as some people complain of greying hair with dutasteride or finasteride. A lack of potent androgens through 5AR inhibition could definitely cause decreased melanocyte function and decreased pigment production.
I just wanted to throw some of this stuff out there as I'm kind of doing some research in my spare time. My next step is to look for a link between male pattern baldness and psoriasis. Afterall, both processes seem to involve hyperkeratinization and it would not surprise me if the underlying cause of psoriasis ends up being somehow linked with androgens.
I'm sure that everyone who is interested already knows about the perifollicular fibrosis and keratinocyte death associated with increased TGF-beta in male pattern baldness patients.
Personally, I think the TGF-beta mechanism is merely the body's way of trying to protect itself from this hyperkeratinization, lack of keratinocyte differentiation, and increased keratinocyte proliferation secondary to increased production of pro-growth IGF-1 due to increased androgen receptor sensitivity in male pattern baldness patients. Unfortunately, the increased TGF-beta also leads to keratinocyte death, decreased collagenase, increased collagen deposition, and a reduction in hair growth. Increased IGF-1 also leads to an increase in the local immune response.
With what I have written down, I can explain how minoxidil, 5AR inhibitors, apple poly, immune suppressants, and nizoral all work. I can also explain why drugs like accutane are the enemy. Lastly, I think that i can explain why male pattern baldness happens on the scalp and not on the rest of the body. The last one might be pushing it, but I might have a pretty good idea.
For everyone else, I'm truly looking for opinions on all this stuff. Don't be shy. There are a lot of good studies that are cited. Use them to further your knowledge base and maybe we can actually find a good treatment instead of dwelling on theories and studies that have been posted more that 5-15 years ago.
If this is supposed to be in the experimental section, would a moderator please move it there. Thank you.
