Localization of androgen receptors in human skin by immunohistochemistry: implications for the hormonal regulation of hair growth, sebaceous glands and sweat glands

Choudhry, R.; Hodgins, Malcolm B.; Kwast, Theo H. van der; Brinkmann, A.O.; Boersma, W.J.A.

doi:10.1677/joe.0.1330467

Cited by 300 publications

(154 citation statements)

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“…Although epidermal basal cells, dermal fibroblasts, and endothelial cells were reported to be positive for androgen receptor in a previous study using polyclonal or monoclonal antibody on frozen tissue sections (Blauer et al, 1991;Choudhry et al, 1992), we could not confirm androgen receptor expression in these cell types. No staining of androgen receptor was observed in normal lymph nodes.…”

Section: Resultscontrasting

confidence: 74%

“…Since normal genital skin contains various cellular components that express androgen receptor (Blauer et al, 1991;Choudhry et al, 1992), we examined expression of androgen receptor mRNA in lymph node samples. As shown in Figure 2, LNCaP cell and 4 metastases that expressed androgen receptor protein showed androgen receptor transcripts with the expected size of 365 bp.…”

Section: Resultsmentioning

confidence: 99%

“…To explore further the molecular pathogenesis of EMPD, we aimed at examining androgen receptor expression in Paget's cells of EMPD for several reasons. Firstly, tumor cells in EMPD show differentiation to apocrine sweat glands (Guarner et al, 1989), which normally express androgen receptor (Blauer et al, 1991;Choudhry et al, 1992;Kurata et al, 1990). Secondly, the androgen receptor is a liganddependent transcriptional factor that regulates tissuespecific genes involved in cellular proliferation and differentiation (Cude et al, 1999).…”

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confidence: 99%

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Expression of Structurally Unaltered Androgen Receptor in Extramammary Paget's Disease

Fujimoto

Takata

Hatta

et al. 2000

Laboratory Investigation

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SUMMARY: Extramammary Paget's disease (EMPD) is an uncommon neoplasm of the skin that shows differentiation to an apocrine sweat gland. Although we previously showed that erbB-2 overexpression may play a part in the progression of EMPD, molecular genetic defects underlying the development of EMPD are poorly understood. In the study described here, we examined androgen receptor expression and gene alterations in 30 cases of EMPD without internal malignancy. Immunohistochemistry revealed that 24 of 30 (80%) cases of EMPD variably expressed nuclear androgen receptor. Semi-quantitation of receptor content by scoring immunostained sections showed no difference between in situ (n ϭ 17) and invasive (n ϭ 13) EMPD tumors. Androgen receptor expression was also observed in four of six lymph node metastases. In these lymph nodes, expression of androgen receptor mRNA was confirmed by reverse transcriptase-polymerase chain reaction. Direct sequencing of exon 2 through exon 8, which encodes DNA-and hormone-binding domains of the androgen receptor gene, revealed no mutation in any of the 10 advanced stage tumors. Neither amplification nor deletion of the androgen receptor gene locus was detected by dual color fluorescence in situ hybridization analysis in 14 tumors. The present findings showing frequent expression of structurally unaltered androgen receptor in an advanced stage of EMPD may provide a rational basis for hormone therapy, which is widely used in the treatment of metastatic prostate cancer and androgen receptor-positive breast cancer recurrence. (Lab Invest 2000, 80:1465-1471.E xtramammary Paget's disease (EMPD) is an uncommon neoplasm of apocrine gland-bearing skin, that most commonly involves the vulvar, perianal, perineal, scrotal, and penile regions (Heymann, 1993). Although it is rarely associated with underlying adenocarcinoma, it mostly begins as an intraepidermal adenocarcinoma that can invade the dermis and may metastasize via the lymphatic system (Feuer et al, 1990;Hart and Millman, 1977;Jones et al, 1979;Murata et al, 1999). The histogenesis of EMPD has long been disputed. Emerging information, however, supports the concepts that Paget's cells in EMPD are of glandular origin, usually showing apocrine differentiation and that the disease may arise from a pluripotential epidermal precursor (Guarner et al, 1989;Mazoujian et al, 1984;Roth et al, 1977).The molecular genetic defects underlying EMPD are poorly understood. We previously showed that erbB-2 overexpression by either gene amplification or transcriptional activation may play a part in the progression of EMPD (Takata et al, 1999). However, other molecular genetic defects, including p53 mutations, allelic loss of several selected chromosome arms as well as abnormal activation of the ␤-catenin gene, which are commonly seen in other epithelial malignancies, were not detected in EMPD (Takata et al, 1999;Takata et al, 1997). To explore further the molecular pathogenesis of EMPD, we aimed at examining androgen receptor expression in Paget's cells of EMPD f...

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Section: Resultscontrasting

confidence: 74%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Expression of Structurally Unaltered Androgen Receptor in Extramammary Paget's Disease

Fujimoto

Takata

Hatta

et al. 2000

Laboratory Investigation

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“…As mentioned previously baldness is androgen dependent, and much of the focus on papilla cells has been because they possess androgen receptors and metabolize androgens. However, as illustrated by Choudry et al (80) dermal sheath cells also posses androgen receptors. Moreover, the sheath is vascularized throughout the follicle cycle.…”

Section: The Dermal Sheathmentioning

confidence: 95%

Cellular and developmental aspects of androgenetic alopecia

Jahoda

1998

Experimental Dermatology

182

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The hair follicle is a highly complex system that can be investigated at many levels and from multiple perspectives. However, underlying the cyclic production of all hair fibres are a set of common developmental processes. Many current investigations of androgenetic alopecia concentrate on the direct influences of hormones on hair follicles at the cellular but the paper also tries to point out inherent difficulties in the investigation of androgenetic alopecia and important gaps in current knowledge.

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“…With respect to hirsutism, androgens are involved in the irreversible transformation of fine vellus hairs into coarse terminal hairs 7 . Androgens also contribute to the pathogenesis of acne vulgaris in that androgen receptors and 5-alpha reductase, the enzyme that transforms testosterone to the more potent dihydrotestosterone (DHT), are both present within the sebaceous follicle 8,9 . Left untreated, hyperandrogenism can lead to long-term psychological sequelae, for example, related to facial scarring from acne 10 .…”

Section: Consequences Of Hyperandrogenismmentioning

confidence: 99%

Statins in the Treatment of Polycystic Ovary Syndrome

Kodaman

Dulęba²

2008

Semin Reprod Med

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Many women of reproductive age are affected by polycystic ovary syndrome (PCOS), a heterogeneous endocrinopathy characterized by androgen excess, chronic oligo-anovulation and/or polycystic ovarian morphology. In addition, PCOS is often associated with insulin resistance, systemic inflammation and oxidative stress which, on one hand, lead to endothelial dysfunction and dyslipidemia with subsequent cardiovascular sequelae and, on the other hand, to hyperplasia of the ovarian theca compartment with resultant hyperandrogenism and anovulation. While traditionally statins have been used to treat dyslipidemia by blocking HMG-CoA reductase, the rate limiting step in cholesterol biosynthesis; in fact, they possess pleiotropic actions, resulting in antioxidant, antiinflammatory and anti-proliferative effects. Statins offer a novel therapeutic approach to PCOS in that they address the dyslipidemia associated with the syndrome, as well as hyperandrogenism/ hyperandrogenemia. These actions may be due to an inhibition of the effects of systemic inflammation and insulin resistance/hyperinsulinemia. Evidence to date, both in vitro and in vivo, suggests that statins have potential in the treatment of PCOS; however, further clinical trials are needed before they can be considered a standard of care in the medical management of this common endocrinopathy.

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Localization of androgen receptors in human skin by immunohistochemistry: implications for the hormonal regulation of hair growth, sebaceous glands and sweat glands

Cited by 300 publications

References 0 publications

Expression of Structurally Unaltered Androgen Receptor in Extramammary Paget's Disease

Expression of Structurally Unaltered Androgen Receptor in Extramammary Paget's Disease

Cellular and developmental aspects of androgenetic alopecia

Statins in the Treatment of Polycystic Ovary Syndrome

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