Androgen Receptors in Bone-Forming Tissue

Abstract

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.

The mutual dependence between bone and gonads

“…The sex steroid hormones may influence skeletal physiology, at least in part, by acting directly on bone cells via their classical receptors for estrogens or androgens (Noble et al 1999, Vidal et al 1999, Bord et al 2001. However, mice deficient for ERa (aERKO), ERb (bERKO), double ER (DERKO), and AR (ARKO) did not produce phenotypes similar to those observed in the absence of estrogen or androgen (Couse & Korach 1999, Couse et al 1999, Oz et al 2000, Vidal et al 2000, Lindberg et al 2001, Riggs et al 2002, Vanderschueren et al 2004, Callewaert et al 2009).…”

Androgen receptor (AR) in osteocytes is important for the maintenance of male skeletal integrity: Evidence from targeted AR disruption in mouse osteocytes

“…AR expression has been shown in a number of bone cells including pluripotent mesenchymal bone marrow stromal cells, osteoblasts, osteoclasts and osteocytes. (6)(7)(8) Osteoblasts are potential targets for androgen action because they contain a high AR expression. (9)(10)(11) Thus far two osteoblastspecific AR knockouts have been generated.…”

Androgen Receptor Expression and Function in Osteoclasts

“…There is evidence that androgens mediate their effect via direct activation of the androgen receptor (AR) in osteoblasts. In support of this, the AR has been identified in human and rat osteoblast-like cells [6,7], normal human osteoblasts in vitro [8] and human and rat bone in situ [9][10][11]. Moreover, we have previously generated genetically modified mice in which the AR is specifically deleted within mature osteoblasts [12].…”

“…Specifically, we performed immunohistochemistry on sections of rat femur to detect AR protein in osteoclasts as well as other bone cell types known to express the AR (i.e. osteoblasts, osteocytes, megakaryocytes [9][10][11]30]). We were unable however, to detect AR mRNA expression in bone cells of the rat femur using in situ hybridisation This is most likely due to the sensitivity of the assay as AR mRNA was detected by in situ hybridisation in the positive control tissue, the testes, which is known to express high levels of AR mRNA while in contrast, the level of AR mRNA in bone is much lower [31].…”