Localisation of Androgen Receptors in Dermal Fibroblasts, Grown in vitro, from Normal Subjects and from Patients with Androgen Insensitivity Syndrome

Jacobson, W.; Routledge, J.; Davies, Helen; Saich, T.; Hughes, I A; Brinkmann, A.O.; Brown, B. D.; Clarkson, Priscilla M.

doi:10.1159/000184598

Cited by 8 publications

(7 citation statements)

References 12 publications

(22 reference statements)

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“…In spite of this it was generally assumed that AR are localised in the nucleus. When we [10]used an immunocytochemical technique on human dermal fibroblasts grown in vitro, almost all AR were found in the cytoplasm and the nuclei were either free from AR or contained very few AR granules, when the culture medium contained no added androgen. In the presence of added androgens some AR were translocated into the nucleus.…”

Section: Discussionmentioning

confidence: 99%

“…Studying the intracellular localisation of the androgen receptor in normal human dermal fibroblasts with an immunocytochemical technique [10], we showed the AR localised to the cytoplasm when the culture medium did not contain added androgen. However, in the presence of added dihydrotestosterone or methyltrienolone some, but not all, AR was translocated to the nucleus, so that the density of AR in the nucleus and in the cytoplasm was similar.…”

Section: Introductionmentioning

confidence: 99%

“…The receptors were stained by a slightly modified technique as used for human dermal fibroblasts [10]. …”

Section: Introductionmentioning

confidence: 99%

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Androgen Receptors in Bone-Forming Tissue

et al. 1999

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Androgen receptors (AR) were stained in sections of normal human growth plate of the costo sternal junction obtained at postmortem from one 4-day-old and two 5-day-old male infants, and in osteoblasts, grown in culture obtained from the femora of 3 male patients undergoing orthopaedic surgery for osteoarthritis. In the growth plate AR were found mostly in a narrow band of chondrocytes occupying an area about midway between the proximal and distal end of the epiphysis. Nearly all AR were in the cytoplasm and appeared in a granular form; there was no diffuse staining and the nuclei were either completely devoid of AR or only contained a few. Less-differentiated chondroblasts, perichondrial cells and hypertrophic chondrocytes contained few or no AR. Osteoblasts (and osteocytes) contained numerous AR and almost all were in the cytoplasm. Normal human osteoblasts, in their second or third passage, were grown on coverslips either in a medium with no added androgen or in the presence of 5α-dihydrotestosterone or methyltrienolone for a period of 24 h or longer. In control cultures, with vehicle and no added androgen, nearly all AR were found in the cytoplasm, with hardly any in the nucleus. In the presence of added androgen some osteoblasts from two of the specimens demonstrated a clear translocation of AR into the nucleus, whilst osteoblasts from a third specimen failed to translocate. These preliminary results indicate that AR translocation to the nucleus occurs in osteoblastic cells derived from osteoarthritic subjects. However, the ability to translocate may depend on the state of differentiation of the osteoblast and on culture conditions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Androgen Receptors in Bone-Forming Tissue

et al. 1999

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“…Although the AR is commonly thought to reside in the nucleus, it has also been suggested that it is localized in the cytoplasm and enters the nucleus via a hormone-dependent import process (25,26). In addition, the cellular localization of the AR may be tissue specific or affected by experimental technique, such as fixation and staining (27). Such contradictory evidence on cellular localization has been reported with other nuclear receptors.…”

Section: Es Cells Have a Functional Armentioning

confidence: 99%

Evidence that Androgens Regulate Early Developmental Events, Prior to Sexual Differentiation

2007

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Androgen signaling is critical for normal fetal development but is not thought to regulate events in early embryogenesis. Given the interest in factors controlling the differentiation of embryonic stem (ES) cells, we have explored the possibility that androgens may play a role. This study demonstrates expression of androgen receptor (AR) RNA and protein in four independent mouse ES (mES) cell lines, and shows that the AR is functional and can interact with transfected androgen response elements to promote green fluorescent protein expression. AR mRNA was detected throughout 10-d differentiation in embryoid bodies (EBs). Exposure of EBs to testosterone (T) or dihydrotestosterone, at doses of 1 and 0.1 mum, respectively, promoted formation of beating cardiomyocytes. Flow cytometric analyses demonstrated a significant increase in the number of alpha-actinin and tropomyosin (cardiac markers) positive cells after these treatments. Addition of flutamide (1 microM) to T-treated EBs inhibited the T-induced proliferation of cardiomyocytes, confirming that, in this instance, androgens act via the classical AR-mediated genomic pathway. We also report that mES cells express key steroidogenic enzymes, as detected by RT-PCR, and during 24-h incubations secrete T at concentrations of 1.38 +/- 0.22 nM, levels comparable to those secreted by cultured Leydig cells. These novel data demonstrate the capacity of androgens to stimulate increased differentiation of mouse ES cells to cardiomyocytes, and are in keeping with recent observations that AR-deficient mice exhibit cardiac impairment in adulthood.

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“…Although significant advances in recent years have been made in both the organ culture of skin (57, 58) and the cell culture of the different cellular components of skin, including epidermal keratinocytes (59), melanocytes (60) and dermal fibroblasts (61), little progress has been made in the investigation of estrogen action in skin tissues.…”

Section: Estrogens and Skinmentioning

confidence: 99%

The biological actions of estrogens on skin

Thornton

2002

Experimental Dermatology

222

157

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There is still extensive disparity in our understanding of how estrogens exert their actions, particularly in non-reproductive tissues such as the skin. Although it has been recognized for some time that estrogens have significant effects on many aspects of skin physiology and pathophysiology, studies on estrogen action in skin have been limited. However, estrogens clearly have an important function in many components of human skin including the epidermis, dermis, vasculature, hair follicle and the sebaceous, eccrine and apocrine glands, having significant roles in skin aging, pigmentation, hair growth, sebum production and skin cancer. The recent discovery of a second intracellular estrogen receptor (ERb) with different cell-specific roles to the classic estrogen receptor (ERa), and the identification of cell surface estrogen

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Localisation of Androgen Receptors in Dermal Fibroblasts, Grown in vitro, from Normal Subjects and from Patients with Androgen Insensitivity Syndrome

Cited by 8 publications

References 12 publications

Androgen Receptors in Bone-Forming Tissue

Androgen Receptors in Bone-Forming Tissue

Evidence that Androgens Regulate Early Developmental Events, Prior to Sexual Differentiation

The biological actions of estrogens on skin

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