Choudhry R, Hodgins MB, Van der Kwast TH, Brinkmann AO, Boersma WJLocalization of androgen receptors in human skin by immunohistochemistry: implications for the hormonal regulation of hair growth, sebaceous glands and sweat glands. J Endocrinol 133:467-475
ABSTRACT A mouse monoclonal antibody against the N-terminal region of human androgen receptor (AR) was used to identify receptors by immunoperoxidase staining in frozen serial sections of skin from scalp, face, limb and genitalia of men and women aged 30-80 years. AR staining was restricted to cell nuclei. In sebaceous glands, AR were identified in basal and differentiating sebocytes. The percentage of receptor-positive basal sebocyte nuclei in the temple/forehead region was greater in males (65%) than in females (29%). AR staining was restricted to the cells of dermal papillae in anagen and telogen hair follicles. The percentage of dermal papillae containing AR was greater in males (58%) than in females (20%). The number of positively stained dermal papillae was lowest in female scalp skin. In 163 hair follicles sectioned, AR were absent from germinative matrix, outer root sheath (including the bulge region), inner root sheath, hair shaft and hair bulb, and from the capillaries present in some large dermal papillae. AR were present in pilosebaceous duct keratinocytes, suggesting that androgens may influence pilosebaceous duct keratinization. AR were also identified in interfollicular epidermal keratinocytes and dermal fibroblasts although, in both cell types, intensity and frequency of staining were greatest in genital skin. AR were identified in luminal epithelial cells of apocrine glands in genital skin and in certain cells of the secretory coils of eccrine sweat glands in all body sites. This study indicates that androgens regulate sebaceous gland and hair growth by acting upon two different types of target cells, the epithelial sebocytes of sebaceous glands and the mesenchymal cells of the hair follicle dermal papilla.(ABSTRACT TRUNCATED AT 250 WORDS)
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- "AR expression level is a crucial factor in determining DPC sensitivity to androgens in AGA . It is known that AR mRNA ,  and protein  are expressed in DPCs. In addition, DPCs isolated from balding area express more AR compared to those in non-balding areas , . "
ABSTRACT: The dermal papilla, located in the hair follicle, expresses androgen receptor and plays an important role in hair growth. Androgen/Androgen receptor actions have been implicated in the pathogenesis of androgenetic alopecia, but the exact mechanism is not well known. Recent studies suggest that balding dermal papilla cells exhibit premature senescence, upregulation of p16 (INK4a) , and nuclear expression of DNA damage markers. To investigate whether androgen/AR signaling influences the premature senescence of dermal papilla cells, we first compared frontal scalp dermal papilla cells of androgenetic alopecia patients with matched normal controls and observed that premature senescence is more prominent in the dermal papilla cells of androgenetic alopecia patients. Exposure of androgen induced premature senescence in dermal papilla cells from non-balding frontal and transitional zone of balding scalp follicles but not in beard follicles. Overexpression of the AR promoted androgen-induced premature senescence in association with p16 (INK4a) upregulation, whereas knockdown of the androgen receptor diminished the effects of androgen. An analysis of γ-H2AX expression in response to androgen/androgen receptor signaling suggested that DNA damage contributes to androgen/androgen receptor-accelerated premature senescence. These results define androgen/androgen receptor signaling as an accelerator of premature senescence in dermal papilla cells and suggest that the androgen/androgen receptor-mediated DNA damage-p16 (INK4a) axis is a potential therapeutic target in the treatment of androgenetic alopecia.PLoS ONE 11/2013; 8(11):e79434. DOI:10.1371/journal.pone.0079434 · 3.23 Impact Factor
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- "The expression of hormonal receptors could have treatment implications since hormonal modulation plays an important role in the prevention and treatment of breast carcinomas . Choudhry et al  reported AR expression in normal apocrine as well as eccrine glands. This suggests that androgen may modulate the function of both apocrine and eccrine glands. "
ABSTRACT: Apocrine-eccrine carcinomas are rare and associated with poor prognosis. Currently there is no uniform treatment guideline. Chemotherapeutic drugs that selectively target cancer-promoting pathways may complement conventional therapeutic approaches. However, studies on genetic alterations and EGFR and Her2 status of apocrine-eccrine carcinomas are few in number. In addition, hormonal studies have not been comprehensive and performed only on certain subsets of apocrine-eccrine carcinomas. To investigate whether apocrine-eccrine carcinomas express hormonal receptors or possess activation of oncogenic pathways that can be targeted by available chemotherapeutic agent we performed immunohistochemistry for AR, PR, ER, EGFR, and HER2 expression; fluorescence in situ hybridization (FISH) for EGFR and ERBB2 gene amplification; and molecular analyses for recurrent mutations in 15 cancer genes including AKT-1, EGFR, PIK3CA, and TP53 on 54 cases of apocrine-eccrine carcinomas. They include 10 apocrine carcinomas, 7 eccrine carcinomas, 9 aggressive digital papillary adenocarcinomas, 10 hidradenocarcinomas, 11 porocarcinomas, 1 adenoid cystic carcinoma, 4 malignant chondroid syringomas, 1 malignant spiradenoma, and 1 malignant cylindroma. AR, ER, PR, EGFR and HER2 expression was seen in 36% (19/53), 27% (14/51), 16% (8/51), 85% (44/52) and 12% (6/52), respectively. Polysomy or trisomy of EGFR was detected by FISH in 30% (14/46). Mutations of AKT-1, PIK3CA, and TP53 were detected in 1, 3, and 7 cases, respectively (11/47, 23%). Additional investigation regarding the potential treatment of rare cases of apocrine-eccrine carcinomas with PI3K/Akt/mTOR pathway inhibitors, currently in clinical testing, may be of clinical interest.PLoS ONE 10/2012; 7(10):e47290. DOI:10.1371/journal.pone.0047290 · 3.23 Impact Factor
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- "It may also be that androgen metabolism is increased at the level of the pilosebaceous unit as well, either independently or dependently on the level of circulating androgens. Androgen receptors have been localized to the outer root sheath of keratinocytes and to the basal layer of the sebaceous gland.13,14 Androgens are thought to stimulate growth and differentiation of sebaceous glands. "
ABSTRACT: Combined oral contraceptive pills (cOCPs) are often used in the treatment of acne in females. They are effective, safe, and easy to use in appropriate patients in combination with more conventional acne therapies. This article will briefly address the physiologic rationale for the use of cOCPs in the treatment of acne. It will also review efficacy by examining relevant clinical trials. Safety considerations and the adverse event profile for oral contraceptives will be presented. Finally, practical considerations for prescribing cOCPs will be discussed.International Journal of Women's Health 08/2010; 2(1):69-76. DOI:10.2147/IJWH.S5915