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Androgens are among the most well studied hormones in cutaneous biology. The classical androgen-dependent dermatoses, acne, androgenetic alopecia (Androgenetic Alopecia), seborrhea and hirsutism are among the most common skin disorders. Human sebaceous glands and hair follicles are equipped with all the necessary enzymes for biosynthesis and metabolism of androgens. Androgens can be generated via de novo synthetic pathway from cholesterol to T and dihydrotestosterone (DHT), or/and via a shortcut pathway from the circulating dehydroepiandrosterone sulfate (DHEAS).[SUP]75[/SUP] Four “upstream” enzymes including steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc) and cytochrome P450 17α-hydroxylase/17,20-lyase (P450c17) and steroid 3β-hydroxysteroid dehydrogenase (3β-HSD) are responsible for the early steps of androgenesis from cholesterol to DHEA, while four additional “downstream” enzymes including steroid sulfatase and 5α-reductase work for the formation of DHT from DHEAS to amplify the androgenic effects, or 3α-HSD and aromatase function to reduce androgen levels.
Androgenetic Alopecia can be defined as a DHT-dependent process with continuous miniaturization of androgen sensitive hair follicles in the frontoparietal scalp. However, as most men with Androgenetic Alopecia, similar to men with acne, have normal circulating levels of androgens, the “cutaneous hyperandrogenism” is hypothesized to be caused by (1) overproduction of androgens in the pilosebaceous units due to enhanced expression and activity of androgenic enzymes, or/and (2) overexpression or hyperresponsiveness of androgen receptors. The former has been supported by the increased expression and enzyme activity of StAR, 3β-HSD, 17β-HSD and 5β-reductase leading to high follicular levels of DHT.[SUP]75[/SUP][SUP],[/SUP][SUP]86[/SUP][SUP],[/SUP][SUP]87[/SUP] Moreover, studies of the cutaneous expression of sex-determining genes in regulating steroidogenesis showed significantly higher protein levels of DAX-1, SRY and WT-1 in the bald fronto-parietal scalp as compared to the occipital scalp, in which only the SRY expression displayed a positive correlation with the baldness severity in Norwood-Hamilton classification.[SUP]88[/SUP] On the other hand, higher levels of AR were found in the balding hair follicle DPC than those from non-balding scalp,[SUP]80[/SUP] and AR polymorphism was suggested to confer susceptibility to Androgenetic Alopecia.[SUP]89[/SUP] Highly interesting are regional differences in cutaneous hyperandrogenism, in which (1) people with acne may not have Androgenetic Alopecia and vice versa; (2) Androgenetic Alopecia involves almost exclusively the frontoparietal scalp sparing the occipital scalp; (3) acne lesions tends to move from forehead/cheeks in pubertal acne to lower face/submandibular regions in acne tarda. There are some explanations for the contradictory androgen actions on hair follicles from different anatomic sites or between men with and without Androgenetic Alopecia: (1) absence of AR in DPC from occipital scalp;[SUP]90[/SUP] (2) the expression of AR co-activator was higher in DPC from beard and bald frontal scalp but lower in cells from occipital scalp;[SUP]91[/SUP] (3) androgen significantly stimulated the proliferation of keratinocytes co-cultured with beard DPC via insulin-like growth factor-I, while the inhibitory effect of androgen on the growth of keratinocytes co-cultured with DPC from Androgenetic Alopecia was mediated by TGFβ1 in a paracrine manner;[SUP]92[/SUP] (4) differences in the expression of specific biomarkers in beard vs. scalp DPC;[SUP]93[/SUP] (5) higher concentrations of DHT and T could cause apoptosis in human DPC from nonbalding occipital scalp;[SUP]94[/SUP] (6) significant suppression of Wnt signal-mediated transcription in response to DHT treatment was observed only in DP cells from Androgenetic Alopecia patients.[SUP]95
[/SUP]
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835896/
Androgenetic Alopecia can be defined as a DHT-dependent process with continuous miniaturization of androgen sensitive hair follicles in the frontoparietal scalp. However, as most men with Androgenetic Alopecia, similar to men with acne, have normal circulating levels of androgens, the “cutaneous hyperandrogenism” is hypothesized to be caused by (1) overproduction of androgens in the pilosebaceous units due to enhanced expression and activity of androgenic enzymes, or/and (2) overexpression or hyperresponsiveness of androgen receptors. The former has been supported by the increased expression and enzyme activity of StAR, 3β-HSD, 17β-HSD and 5β-reductase leading to high follicular levels of DHT.[SUP]75[/SUP][SUP],[/SUP][SUP]86[/SUP][SUP],[/SUP][SUP]87[/SUP] Moreover, studies of the cutaneous expression of sex-determining genes in regulating steroidogenesis showed significantly higher protein levels of DAX-1, SRY and WT-1 in the bald fronto-parietal scalp as compared to the occipital scalp, in which only the SRY expression displayed a positive correlation with the baldness severity in Norwood-Hamilton classification.[SUP]88[/SUP] On the other hand, higher levels of AR were found in the balding hair follicle DPC than those from non-balding scalp,[SUP]80[/SUP] and AR polymorphism was suggested to confer susceptibility to Androgenetic Alopecia.[SUP]89[/SUP] Highly interesting are regional differences in cutaneous hyperandrogenism, in which (1) people with acne may not have Androgenetic Alopecia and vice versa; (2) Androgenetic Alopecia involves almost exclusively the frontoparietal scalp sparing the occipital scalp; (3) acne lesions tends to move from forehead/cheeks in pubertal acne to lower face/submandibular regions in acne tarda. There are some explanations for the contradictory androgen actions on hair follicles from different anatomic sites or between men with and without Androgenetic Alopecia: (1) absence of AR in DPC from occipital scalp;[SUP]90[/SUP] (2) the expression of AR co-activator was higher in DPC from beard and bald frontal scalp but lower in cells from occipital scalp;[SUP]91[/SUP] (3) androgen significantly stimulated the proliferation of keratinocytes co-cultured with beard DPC via insulin-like growth factor-I, while the inhibitory effect of androgen on the growth of keratinocytes co-cultured with DPC from Androgenetic Alopecia was mediated by TGFβ1 in a paracrine manner;[SUP]92[/SUP] (4) differences in the expression of specific biomarkers in beard vs. scalp DPC;[SUP]93[/SUP] (5) higher concentrations of DHT and T could cause apoptosis in human DPC from nonbalding occipital scalp;[SUP]94[/SUP] (6) significant suppression of Wnt signal-mediated transcription in response to DHT treatment was observed only in DP cells from Androgenetic Alopecia patients.[SUP]95
[/SUP]
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835896/