Testosterone inhibits osteoclast formation stimulated by parathyroid hormone through androgen receptor

Chen, Qingxiang; Kaji, Hiroshi; Sugimoto, Toshitsugu; Chihara, Kazuo

doi:10.1016/s0014-5793(01)02160-3

Cited by 56 publications

(49 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, the global AR null model also develops late onset obesity [15]. Finally, recent publications document that androgen can directly reduce bone resorption of isolated osteoclasts [45], inhibits osteoclast formation stimulated by PTH [10], and may play a direct role regulating aspects of osteoclast activity in conditional AR null mice [40]. Our results suggest that at least some component of inhibition of osteoclastic resorptive activity as a consequence of androgen administration is mediated indirectly through effects on mature osteoblasts and osteocytes.…”

Section: Discussionmentioning

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

Section: Discussionmentioning

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

show abstract

“…Normal male rats have androgens like testosterone, dihydrotestosterone (DHT) and non-aromatizable androgens which were able to suppress the osteoclast formation (33) and increase the osteoblast proliferation to maintain bone density (34,35). The protective role of androgens in bone regulation was supported by other studies (36,37,38,39). Estrogen was also shown to play an important role in maintaining the bone density in males (40).…”

Section: Discussionmentioning

confidence: 94%

Keloid of ear lobes: nature's ear rings

2009

IJPS

View full text Add to dashboard Cite

Vitamin E has been shown to have anabolic action on bone of normal male rats. The presence of vitamin E in palm and soy oil, the commonly used plant-derived frying oils have rendered them more resistant to oxidation when repeatedly heated. Previous studies have shown that repeatedly heated frying oils had caused bone loss in ovariectomised rats. This was believed to be contributed by the generation of free radicals in the heated frying oils. Our study aimed to evaluate the effects of repeatedly heated palm and soy oils on the bone of normal male rats. Methods: Forty-two male Sprague-Dawley rats were randomly assigned into seven groups according to their diet; normal control (NC), fresh palm oil (FPO), fresh soy oil (FSO), five times heated palm oil (5HPO), five times heated soy oil (5HSO), ten times heated palm oil (10HPO) and ten times heated soy oil (10HSO). The rats were fed for six months with rat chow mixed with the respective oils at 15% (w/w). Bone structural changes were assessed by performing histomorphometry on the rat femora. The parameters measured were Trabecular volume (BV/TV), Trabecular thickness (TbTh), Trabecular separation (TbSp) and Trabecular Number (TbN). Results: There were no significant differences in all the structural histomorphometric parameters of the repeatedly heated oils groups when compared to normal control and fresh oils groups. Conclusion: Repeatedly heated palm and soy oils are safe and not detrimental to the bone structure of normal male rats. The vitamin E content in the oils may be responsible for these bone protective effects.

show abstract

“…Numerous in vitro, in vivo and human clinical studies have evidenced the substantial anti-osteoporotic efficacy of 5α-DHT and their roles in the regulation of skeletal homeostasis [15][16][17][18][19][20]. Chen et al [17] demonstrated that 5α-DHT inhibits osteoclast formation, differentiation and maturation by blocking androgen receptors. The involvement and prime importance of androgen receptors and estrogen receptors has also been critically discussed by Mohamed et al [21].…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have evidenced the substantial roles of androgens (dihydrotestosterone) in the regulation of skeletal homeostasis in humans [15,16] and rodents [17][18][19][20]. According to a recently published review [21], testosterone imparts promising roles in improving the bone health by enhancing the proliferation and differentiation of osteoblasts and down-regulating the maturation of osteoclasts.…”

Section: Introductionmentioning

confidence: 99%

Dihydrotestosterone Downregulates Bone Resorption Activity of Osteoclasts in Dose Dependent Manner: An in Vitro Model Using Raw 264.7 Cells

Thu

Hussain

Mohamed

et al. 2017

Int J Pharm Pharm Sci

View full text Add to dashboard Cite

Objective: Numerous studies have evidenced the bone regulatory potential of dihydrotestosterone in androgen-deficient osteoporosis. The present study was thus aimed to explore the translational mechanism of dihydrotestosterone to down-regulate the bone resorption activity of osteoclasts using RAW 264.7 cells as in vitro model. Methods:Prior to analyze the efficacy of dihydrotestosterone (5α-DHT) to alleviate osteoclastic differentiation, their cell viability and cell proliferative ability was assessed using lactate dehydrogenase (LDH) and MTS assays. The osteoclastic differentiation capacity of dihydrotestosterone was evaluated by measuring TRAP activity and the expression of bone resorption-related proteins such as matrix metallopeptidase-9 (MMP-9), cathepsin-K, tartrate-resistant acid phosphatase (TRAP) and NFATc1. Moreover, the effects of dihydrotestosterone were also evaluated on superoxide (free radicals) generation and superoxide dismutase (SOD) activity in RANKL-induced osteoclasts.Results: Dihydrotestosterone showed no toxicity towards RAW 264.7 cells and significantly enhanced their proliferation and growth rates in a dose-dependent fashion. It was also observed that dihydrotestosterone exhibits a remarkable inhibitory effect on differentiation, maturation and activation of osteoclasts. The marked inhibition of differentiation and activation of osteoclasts caused by 5α-DHT was due to down-regulation of the expression of MMP-9, cathepsin-K, TRAP, NFATc1, generation of superoxide and up-regulation of SOD activity in the RAW 264.7 cells. Conclusion:Resulting data provided substantially in vitro evidence for the pronounced anti-osteoclastogenetic activity of dihydrotestosterone and its therapeutic value in treating osteoporosis and other bone-erosive disorders.

show abstract

Testosterone inhibits osteoclast formation stimulated by parathyroid hormone through androgen receptor

Cited by 56 publications

References 25 publications

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

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

Keloid of ear lobes: nature's ear rings

Dihydrotestosterone Downregulates Bone Resorption Activity of Osteoclasts in Dose Dependent Manner: An in Vitro Model Using Raw 264.7 Cells

Contact Info

Product

Resources

About