Gender differences in expression of androgen receptor in tibial growth plate and metaphyseal bone of the rat

Eerden, Bram C. J. van der; Til, Niek P. van; Brinkmann, Albert O.; Löwik, Clemens W.G.M.; Wit, Jan M.; Karperien, Marcel

doi:10.1016/s8756-3282(02)00723-8

Cited by 63 publications

(49 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In situ hybridization was carried out as described previously (van der Eerden et al, 2002) with some modifications. Briefly, sections were deparaffinized, fixed for 10 min in 4% paraformaldehyde (PFA), incubated in 10 mg/ml proteinase K (Qiagen, Chatsworth, CA) in PBS for 10 min at room temperature.…”

Section: Tissue Preparation and Processing For In Situ Hybridizationmentioning

confidence: 99%

Novel type II collagen reporter mice: New tool for assessing collagen 2α1 expression in vivo and in vitro

Tryfonidou

Lunstrum

Hendriks

et al. 2011

Developmental Dynamics

View full text Add to dashboard Cite

We report the generation of a new mouse strain harboring a Col2-pd2EGFP reporter transgene; pd2EGFP has a much shorter half-life than EGFP, making it a near real-time reporter for Col2a1 expression in vivo and in vitro. In the post-natal growth plate, pd2EGFP fluorescence was expressed in almost all proliferative chondrocytes and in some hypertrophic chondrocytes based on localization with type X collagen. In articular cartilage, pd2EGFP fluorescence diminished over time, nicely illustrating the decrease of type II collagen synthesis in articular chondrocytes during growth. Monolayers of FACS-sorted chondrocytes from P1-2 mice showed faster loss of pd2EGFP compared to EGFP, reflecting rapid chondrocyte de-differentiation. High-density culture of FACS-pd2EGFP-growth plate chondrocytes revealed the typical temporal expression pattern in which type II collagen preceded type X collagen matrix deposition. The Col2-pd2EGFP reporter mouse will be a valuable tool for studies of growth plate chondrocyte biology.

show abstract

Section: Tissue Preparation and Processing For In Situ Hybridizationmentioning

confidence: 99%

Novel type II collagen reporter mice: New tool for assessing collagen 2α1 expression in vivo and in vitro

Tryfonidou

Lunstrum

Hendriks

et al. 2011

Developmental Dynamics

View full text Add to dashboard Cite

show abstract

“…Nonetheless, bone is a direct target tissue with respect to androgen action. AR is expressed in the cell types required for skeletal formation and homeostasis, including mesenchymal stromal precursors [4], osteoblasts [1], osteocytes [1,64] and osteoclasts [57]. An additional complication for interpretation of the direct effects of testosterone results from the consequences of its metabolism.…”

Section: Introductionmentioning

confidence: 99%

Targeting of androgen receptor in bone reveals a lack of androgen anabolic action and inhibition of osteogenesis

Wiren

Semirale

Zhang

et al. 2008

Bone

View full text Add to dashboard Cite

Androgens are anabolic hormones that affect many tissues, including bone. However, an anabolic effect of androgen treatment on bone in eugonadal subjects has not been observed and clinical trials have been disappointing. The androgen receptor (AR) mediates biological responses to androgens. In bone tissue, both AR and the estrogen receptor (ER) are expressed. Since androgens can be converted into estrogen, the specific role of the AR in maintenance of skeletal homoeostasis remains controversial. The goal of this study was to use skeletally targeted overexpression of AR in differentiated osteoblasts as a means of elucidating the specific role(s) for AR transactivation in the mature bone compartment. Transgenic mice overexpressing AR under the control of the 2.3-kb α1 (I)-collagen promoter fragment showed no difference in body composition, testosterone, or 17β-estradiol levels. However, transgenic males have reduced serum osteocalcin, CTx and TRAPC5b levels, and a bone phenotype was observed. In cortical bone, high-resolution micro-computed tomography revealed no difference in periosteal perimeter but a significant reduction in cortical bone area due to an enlarged marrow cavity. Endocortical bone formation rate was also significantly inhibited. Biomechanical analyses showed decreased whole bone strength and quality, with significant reductions in all parameters tested. Trabecular morphology was altered, with increased bone volume comprised of more trabeculae that were closer together but not thicker. Expression of genes involved in bone formation and bone resorption was significantly reduced. The consequences of androgen action are compartment-specific; anabolic effects are exhibited exclusively at periosteal surfaces, but in mature osteoblasts androgens inhibited osteogenesis with detrimental effects on matrix quality, bone fragility and whole bone strength. Thus, the present data demonstrate that enhanced androgen signaling targeted to bone results in low bone turnover and inhibition of bone formation by differentiated osteoblasts. These results indicate that direct androgen action in mature osteoblasts is not anabolic, and raise concerns regarding anabolic steroid abuse in the developing skeleton or high-dose treatment in eugonadal adults.

show abstract

“…However, the role played by the locally produced estrogen and androgens within the epiphyseal growth plate (EGP) remains unclear. A direct regulatory role of androgens and estrogens has been suggested by the presence of the androgen receptor (AR) (Colvard et al 1989, Van der Eerden et al 2002b) and both estrogen receptors, ER and ER , in growth plate tissue at the mRNA and protein level in several species, including rats, rabbits and humans (Kusek et al 1998, Kennedy et al 1999, Nilsson et al 1999, Braidman et al 2001, Van der Eerden et al 2002a,b, Batra et al 2003. There are also two reported cases of impaired local estrogen activity due to an estrogen receptor deficiency (Smith et al 1994) or an aromatase deficiency (Morishima et al 1995) in association with delayed skeletal growth.…”

Section: Introductionmentioning

confidence: 99%

The aromatase inhibitor letrozole increases epiphyseal growth plate height and tibial length in peripubertal male mice

Eshet

Maor²,

Ari³

et al. 2004

Journal of Endocrinology

View full text Add to dashboard Cite

Sex hormones may influence longitudinal growth, either indirectly, by affecting the growth-hormone-insulin-like growth factor I (IGF-I) axis, or directly, by affecting changes within the epiphyseal growth plate (EGP). The aim of the present study was to investigate the effects of letrozole, an aromatase inhibitor, on longitudinal growth and changes in the EGP in vivo. Eighteen peripubertal male mice were divided into three groups. The first group was killed at baseline, the second was injected with letrozole (Femara) s.c., 2 mg/kg body weight/day, for 10 days, and the third was injected with the vehicle alone. Serum testosterone levels were found to be significantly higher in the treated group than in the controls. Letrozole induced a significant increase in body weight, tail length and serum growth hormone level, but had no significant effect on the level of serum IGF-I. On histomorphometric study, there was a significant increase (12%) in EGP height in the treated animals compared with controls. Immunohistochemistry showed a 3·4-fold letrozole-induced increase in the proliferation of the EGP chondrocytes, as estimated by the number of proliferation cell nuclear antigen-stained cells, and a decrease in the differentiation of the EGP chondrocytes, as estimated by type X collagen staining. Letrozole did not interfere with type II collagen levels. The study group also showed a twofold increase in the number of IGF-I receptor-positive cells compared with controls. In conclusion, the aromatase inhibitor, letrozole, appears to increase the linear growth potential of the EGP in mice.

show abstract

Gender differences in expression of androgen receptor in tibial growth plate and metaphyseal bone of the rat

Cited by 63 publications

References 26 publications

Novel type II collagen reporter mice: New tool for assessing collagen 2α1 expression in vivo and in vitro

Novel type II collagen reporter mice: New tool for assessing collagen 2α1 expression in vivo and in vitro

Targeting of androgen receptor in bone reveals a lack of androgen anabolic action and inhibition of osteogenesis

The aromatase inhibitor letrozole increases epiphyseal growth plate height and tibial length in peripubertal male mice

Contact Info

Product

Resources

About