Testosterone metabolism in human bone

Schweikert, H. U.; Rulf, W.; Niederle, N.; Schäfer, H.; Keck, E.; Krück, F.

doi:10.1530/acta.0.0950258

Cited by 97 publications

(23 citation statements)

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“…Finally, exogenous administration of DHEA reduced cancellous bone osteopenia in oophorectomized rats [42]. The mechanism through which DHEAS mediates its effects on bone is currently unknown, but could include direct or indirect modulation of hormonal mechanisms [43]. Our data suggest that DHEAS promotes osteoblast activity which was not due to increased cellular carnitine concentration, increased energy metabolism, or differences in cell viability.…”

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confidence: 59%

Carnitine and Dehydroepiandrosterone Sulfate Induce Protein Synthesis in Porcine Primary Osteoblast-Like Cells

et al. 1999

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Abstract. Age-related bone loss eventually leads to osteopenia in men and women. The etiology of age-related bone loss is currently unknown; however, decreased osteoblast activity contributes to this phenomenon. In turn, osteoblast proliferation and function is dependent on energy production, thus the loss of energy production that occurs with age may account for the deficient osteoblast activity. Carnitine and dehydroepiandrosterone-sulfate (DHEAS), both of which decline with age, promote energy production through fatty acid metabolism. Thus, we hypothesized that carnitine and DHEAS would increase osteoblast activity in vitro. Accordingly, we measured the effect of carnitine and DHEAS on palmitic acid oxidation as a measure of energy production, and alkaline phosphatase (ALP) activity and collagen type I (COL) as indices of osteoblast function in primary porcine osteoblast-like cell cultures. Carnitine (10 −3 and 10 −1 M) but not DHEAS (10 −9 , 10 −8 , and 10 −7 M) increased carnitine levels within the cells. Carnitine alone and in combination with DHEAS increased palmitic acid oxidation. Both carnitine and DHEAS alone and in an additive fashion increased ALP activity and COL levels. These results demonstrate that in osteoblast-like cells in vitro, energy production can be increased by carnitine and osteoblast protein production can be increased by both carnitine and DHEAS. These data suggest that carnitine and DHEAS supplementation in the elderly may stimulate osteoblast activity and decrease age-related bone loss. Key words:Osteoblast -Carnitine -Dehydroepiandrosterone sulfate -Alkaline phosphatase -Collagen Type I.Bone loss is often divided into two broad mechanisms: (1) postmenopausal bone loss, characterized by increased osteoclast activity, and (2) age-related bone loss, characterized by decreased osteoblast activity. Osteoblast activity is dependent on energy production. Thus, it is plausible that the loss of energy production, which accompanies age, may account for decreased osteoblast activity. Most cells use both glucose and fatty acid oxidation pathways for ATP synthesis, although some cell types show a substrate preference. For instance, some studies have suggested that glucose is the major fuel substrate for bone [1,2]. However, more recent work indicates that cell populations enriched with osteoblast-like cells generate 40-80% of the energy demands through fatty acid oxidation [3]. Osteoblasts are responsible for bone formation and it follows that they maintain a high rate of ATP utilization to support the requisite protein synthesis. Cells with a high rate of protein synthesis generate ATP from fatty acid oxidation, the most efficient metabolic process for energy production [4][5][6]. Thus, modulation of fatty acid oxidation may regulate the amount of energy available for protein synthesis in osteoblasts.A number of factors are required for fatty acid oxidation. For example, carnitine is the requisite carrier for the transport of long-chain fatty acids across the inner mitochondrial membrane into...

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confidence: 59%

Carnitine and Dehydroepiandrosterone Sulfate Induce Protein Synthesis in Porcine Primary Osteoblast-Like Cells

et al. 1999

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“…However, the mechanism of androgen action on bone metabolism remains controversial. Some studies suggest that the effect is mainly through the effects of aromatase to transform the androgen to estrogen (19). Other studies show that administration of anti-androgens, including flutamide and casodex, to female mice resulted in osteopenia, suggesting the direct role of AR in bone metabolism (20,21).…”

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confidence: 99%

Generation and characterization of androgen receptor knockout (ARKO) mice: An in vivo model for the study of androgen functions in selective tissues

Yeh

Tsai

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

599

456

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By using a cre-lox conditional knockout strategy, we report here the generation of androgen receptor knockout (ARKO) mice. Phenotype analysis shows that ARKO male mice have a female-like appearance and body weight. Their testes are 80% smaller and serum testosterone concentrations are lower than in wild-type (wt) mice. Spermatogenesis is arrested at pachytene spermatocytes. The number and size of adipocytes are also different between the wt and ARKO mice. Cancellous bone volumes of ARKO male mice are reduced compared with wt littermates. In addition, we found the average number of pups per litter in homologous and heterozygous ARKO female mice is lower than in wt female mice, suggesting potential defects in female fertility and/or ovulation. The cre-lox ARKO mouse provides a much-needed in vivo animal model to study androgen functions in the selective androgen target tissues in female or male mice

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“…[21][22][23] Indeed, they suggest that the hOBs could play a role in the gelatin zymography was performed. Activity of the MMP2 and MMP9 was detected as bands on zymograms (Fig.…”

Section: Resultsmentioning

confidence: 99%

Interactions between human osteoblasts and prostate cancer cells in a novel 3D in vitro model

Sieh

Lubik²,

Clements³

et al. 2010

Organogenesis

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Testosterone metabolism in human bone

Cited by 97 publications

References 0 publications

Carnitine and Dehydroepiandrosterone Sulfate Induce Protein Synthesis in Porcine Primary Osteoblast-Like Cells

Carnitine and Dehydroepiandrosterone Sulfate Induce Protein Synthesis in Porcine Primary Osteoblast-Like Cells

Generation and characterization of androgen receptor knockout (ARKO) mice: An in vivo model for the study of androgen functions in selective tissues

Interactions between human osteoblasts and prostate cancer cells in a novel 3D in vitro model

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