Localization of androgen receptors in human skin by immunohistochemistry: implications for the hormonal regulation of hair growth, sebaceous glands and sweat glands.
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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ABSTRACT: Testosterone is an endocrine hormone with functions in the reproductive organs, anabolic events and skin homeostasis. We report here that GPRC6A serves as a sensor and mediator of the rapid action of testosterone in epidermal keratinocytes. The silencing of GPRC6A inhibited testosterone-induced intracellular calcium ([Ca2+]i) mobilization and H2O2 generation. These results indicated that a testosterone-GPRC6A complex is required for the activation of Gq protein, IP3 generation, and [Ca2+]i mobilization, leading to Duox1 activation. H2O2 generation by testosterone stimulated the apoptosis of keratinocytes through the activation of caspase-3. The application of testosterone into 3-D skin equivalents increased the apoptosis of keratinocytes between the granular and stratified corneum layers. These results support an understanding of the molecular mechanism of testosterone-dependent apoptosis in which testosterone stimulates H2O2 generation through the activation of Duox1.Journal of Biological Chemistry 08/2014; · 4.60 Impact Factor
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ABSTRACT: The pathogenesis of acne (the most common disorder involving the sebaceous gland) originates from increased sebum production by the sebaceous gland followed by colonization of the hair follicle with Propionibacterium acnes, hyperkeratinization of the upper follicle, and release of inflammatory mediators into the skin. Androgens are the main stimulators of sebum production. Androgens originate from the gonads and adrenal glands, but can also be locally produced within the sebaceous gland from dehydroepiandrosterone sulfate. In the presence of high androgen levels, which can be either a normal pattern of adolescence or a consequence of gonadal or adrenal disease, overproduction of sebum triggers the pathogenesis of acne which, mainly in adolescent women, has deleterious psychological consequences. Estrogens exert the opposite action on sebum production, probably due to the reduction of androgen availability, a direct consequence of estrogen-related increased production of hepatic sex hormone-binding globulin (SHBG). The inhibition of the hypothalamus-pituitary axis induced by oral contra-ceptives is followed by reduced androgen production. Oral contraceptives containing ethinyl estradiol, which has strong estrogenic activity, amplify the hypoandrogenic effect via estrogen-related stimulation of SHBG. The hypoandrogenic effect of oral contraceptives is modulated by the progestin compound. Progestins derived from 19-nortestosterone bind androgenic receptors, whereas others exert antiandrogenic properties by antagonizing the binding of androgens to their receptors, reduce 5α-reductase, and do not bind SHBG. Through this last effect, SHBG is freely available to bind androgens, and the same progestin is totally free to exert its antian-drogenic properties. After correct evaluation of the cause of acne, appropriate management can be undertaken using oral contraceptives containing low daily doses of ethinyl estradiol (20 or 30 µg) associated with a progestin compound, such as cyproterone acetate, drospirenone, or chlormadinone acetate, the antiandrogenic activity of which has been demonstrated by many studies in animals and in humans.Open Access Journal of Contraception 01/2011;
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ABSTRACT: Abstract Skin tags (STs) are benign connective tissue tumors of the dermis. Several clinical observations suggested the involvement of sex steroids in their development. This study aimed at investigating the possible role of androgen receptor (AR) and estrogen receptors (ERs) in STs pathogenesis through their immunohistochemical (IHC) localization in skin biopsies of this disease and to correlate their expression with different clinical and histopathological parameters. Using IHC techniques, we examined 62 cases with STs and 30 gender- and age-matched, healthy subjects, representing the control group. ERα, ERβ, and AR were upregulated in STs compared to normal skin in epidermis and dermis (p < .001 for all). Higher AR H score was significantly associated with axillary STs (p = .02), skin colored tags (p = .03), acanthosis, and papillomatosis (p = .04 for both). Higher ERα H score was significantly associated with hyperpigmented tags (p < .001) and positive family history (p = .003). Higher ERβ H score was significantly associated with female gender and obesity (p = .004 for both). Higher ERα and AR H scores were significantly associated with loose collagen arrangement (p = .02, p = .004, respectively). Higher AR, ERα, and ERβ H scores were significantly associated with the presence of mast cells (p = .01, p = .04, p = .002, respectively) and dilated blood vessels (p = .006, p = .04, p = .04, respectively). In conclusion, AR and ERs may share in STs pathogenesis through their effect on keratinocytes, fibroblasts, and mast cells.Ultrastructural Pathology 05/2014; · 1.13 Impact Factor