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34247603109
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Gonadal steroids and bone metabolism in men
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This review gives an overview of the recent findings on the key role of androgens and estrogens in male bone metabolism
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Leder B. Gonadal steroids and bone metabolism in men. Curr Opin Endocrinol Diabetes Obes 2007; 14:241-246. This review gives an overview of the recent findings on the key role of androgens and estrogens in male bone metabolism.
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(2007)
Curr Opin Endocrinol Diabetes Obes
, vol.14
, pp. 241-246
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Leder, B.1
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3
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34247579807
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Estrogen metabolism modulates bone density in men
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Napoli N, Faccio R, Shrestha V, et al. Estrogen metabolism modulates bone density in men. Calcif Tissue Int 2007; 80:227-232.
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(2007)
Calcif Tissue Int
, vol.80
, pp. 227-232
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Napoli, N.1
Faccio, R.2
Shrestha, V.3
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4
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33847704966
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Adiposity, estradiol, and genetic variants of steroid-metabolizing enzymes as determinants of bone mineral density
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Zarrabeitia MT, Hernandez JL, Valero C, et al. Adiposity, estradiol, and genetic variants of steroid-metabolizing enzymes as determinants of bone mineral density. Eur J Endocrinol 2007; 156:117-122.
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(2007)
Eur J Endocrinol
, vol.156
, pp. 117-122
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Zarrabeitia, M.T.1
Hernandez, J.L.2
Valero, C.3
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5
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34249059396
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Rochira V, Zirilli L, Madeo B, et al. Skeletal effects of long-term estrogen and testosterone replacement treatment in a man with congenital aromatase deficiency: evidences of a priming effect of estrogen for sex steroids action on bone. Bone 2007; 40:1662-1668. The aim of this study was to provide additional data on the relative roles of androgens and estrogens in male bone metabolism. Only the combined treatment of testosterone and estradiol led to optimal parameters suggesting that testosterone needs estrogens as a permissive factor for a direct androgen anabolic action on bone in men.
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Rochira V, Zirilli L, Madeo B, et al. Skeletal effects of long-term estrogen and testosterone replacement treatment in a man with congenital aromatase deficiency: evidences of a priming effect of estrogen for sex steroids action on bone. Bone 2007; 40:1662-1668. The aim of this study was to provide additional data on the relative roles of androgens and estrogens in male bone metabolism. Only the combined treatment of testosterone and estradiol led to optimal parameters suggesting that testosterone needs estrogens as a permissive factor for a direct androgen anabolic action on bone in men.
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8
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0041923632
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Suppressive function of androgen receptor in bone resorption
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Kawano H, Sato T, Yamada T, et al. Suppressive function of androgen receptor in bone resorption. Proc Natl Acad Sci U S A 2003; 100:9416-9421.
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(2003)
Proc Natl Acad Sci U S A
, vol.100
, pp. 9416-9421
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Kawano, H.1
Sato, T.2
Yamada, T.3
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9
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33645329097
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Relative impact of androgen and estrogen receptor activation in the effects of androgens on trabecular and cortical bone in growing male mice: A study in the androgen receptor knockout mouse model
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Venken K, De Gendt K, Boonen S, et al. Relative impact of androgen and estrogen receptor activation in the effects of androgens on trabecular and cortical bone in growing male mice: a study in the androgen receptor knockout mouse model. J Bone Miner Res 2006; 21:576-585.
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(2006)
J Bone Miner Res
, vol.21
, pp. 576-585
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Venken, K.1
De Gendt, K.2
Boonen, S.3
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10
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34547111836
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Armstrong VJ, Muzylak M, Sunters A, et al. Wnt/beta-catenin signaling is a component of osteoblastic bone cell early responses to load-bearing and requires estrogen receptor alpha. J Biol Chem 2007; 282:20715-20727. This study suggested that Wnt/beta-catenin signalling contributes to bone cell early responses to mechanical strain and that its effectiveness requires ERa. Reduced effectiveness of bone cell responses to bone loading, associated with estrogen-related decline in ERa, may contribute to the failure to maintain structurally appropriate bone mass in osteoporosis in both men and women.
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Armstrong VJ, Muzylak M, Sunters A, et al. Wnt/beta-catenin signaling is a component of osteoblastic bone cell early responses to load-bearing and requires estrogen receptor alpha. J Biol Chem 2007; 282:20715-20727. This study suggested that Wnt/beta-catenin signalling contributes to bone cell early responses to mechanical strain and that its effectiveness requires ERa. Reduced effectiveness of bone cell responses to bone loading, associated with estrogen-related decline in ERa, may contribute to the failure to maintain structurally appropriate bone mass in osteoporosis in both men and women.
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11
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34548074165
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Lorentzon M, Eriksson AL, Nilsson S, et al. Association between physical activity and BMD in young men is modulated by catechol-O- methyltransferase (COMT) genotype: the GOOD study. J Bone Miner Res 2007; 22:1165-1172. COMT is involved in the degradation of estrogens. The aim of this study was to determine if the COMT val158met polymorphism modulates the association between physical activity and bone mineral density (BMD) in young men. The COMT polymorphism was associated with areal BMD, at all sites and with trabecular volumetric BMD in the low-physical activity subjects, but not in their high-physical activity counterparts.
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Lorentzon M, Eriksson AL, Nilsson S, et al. Association between physical activity and BMD in young men is modulated by catechol-O- methyltransferase (COMT) genotype: the GOOD study. J Bone Miner Res 2007; 22:1165-1172. COMT is involved in the degradation of estrogens. The aim of this study was to determine if the COMT val158met polymorphism modulates the association between physical activity and bone mineral density (BMD) in young men. The COMT polymorphism was associated with areal BMD, at all sites and with trabecular volumetric BMD in the low-physical activity subjects, but not in their high-physical activity counterparts.
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12
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34548793630
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Sex steroid levels and cortical bone size in young men are associated with a uridine diphosphate glucuronosyltransferase 2B7 polymorphism (H268Y)
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Swanson C, Lorentzon M, Vandenput L. Sex steroid levels and cortical bone size in young men are associated with a uridine diphosphate glucuronosyltransferase 2B7 polymorphism (H268Y). J Clin Endocrinol Metab 2007;92:3697-3704.
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(2007)
J Clin Endocrinol Metab
, vol.92
, pp. 3697-3704
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Swanson, C.1
Lorentzon, M.2
Vandenput, L.3
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13
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33846900615
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Kousteni S, Almeida M, Han L, et al. Induction of osteoblast differentiation by selective activation of kinase-mediated actions of the estrogen receptor. Mol Cell Biol 2007; 27:1516-1530. This study revealed the existence of a large signalosome in which input from the estrogen receptor, kinases, bone morphogenetic proteins and Wnt signalling converge to induce differentiation of osteoblast precursors. Estrogen receptor can either induce or repress it, depending on whether the activating ligand (and presumably the resulting conformation of the receptor protein) precludes or accommodates ERE-mediated transcription.
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Kousteni S, Almeida M, Han L, et al. Induction of osteoblast differentiation by selective activation of kinase-mediated actions of the estrogen receptor. Mol Cell Biol 2007; 27:1516-1530. This study revealed the existence of a large signalosome in which input from the estrogen receptor, kinases, bone morphogenetic proteins and Wnt signalling converge to induce differentiation of osteoblast precursors. Estrogen receptor can either induce or repress it, depending on whether the activating ligand (and presumably the resulting conformation of the receptor protein) precludes or accommodates ERE-mediated transcription.
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15
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33748312090
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Bone protection by estrens occurs through nontissue-selective activation of the androgen receptor
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Windahl SH, Galien R, Chiusaroli R, et al. Bone protection by estrens occurs through nontissue-selective activation of the androgen receptor. J Clin Invest 2006; 116:2500-2509.
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(2006)
J Clin Invest
, vol.116
, pp. 2500-2509
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Windahl, S.H.1
Galien, R.2
Chiusaroli, R.3
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16
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36348986738
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Identification of target cells for the genomic effects of estrogens in bone
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This study identified the target cells for the genomic effects of estrogens on bone and showed that hypertrophic chondrocytes, megakaryocytes, osteoblasts and lining cells respond to estrogen through the classical ERE-mediated genomic pathway
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Windahl SH, Lagerquist MK, Andersson N, et al. Identification of target cells for the genomic effects of estrogens in bone. Endocrinology 2007; 148:5688-5695. This study identified the target cells for the genomic effects of estrogens on bone and showed that hypertrophic chondrocytes, megakaryocytes, osteoblasts and lining cells respond to estrogen through the classical ERE-mediated genomic pathway.
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(2007)
Endocrinology
, vol.148
, pp. 5688-5695
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Windahl, S.H.1
Lagerquist, M.K.2
Andersson, N.3
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17
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37249081165
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Liu XH, Kirschenbaum A, Yao S, Levine AC. Androgens promote preosteoblast differentiation via activation of the canonical Wnt signaling pathway. Ann N Y Acad Sci 2007 [Epub ahead of print] The nonaromatisable androgen dihydrotestosterone (DHT) significantly stimulates MC3T3preosteoblast differentiation with no effect on cell growth in this in-vitro study. This effect of DHT was accompanied by increased Wnt signalling in the same cells.
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Liu XH, Kirschenbaum A, Yao S, Levine AC. Androgens promote preosteoblast differentiation via activation of the canonical Wnt signaling pathway. Ann N Y Acad Sci 2007 [Epub ahead of print] The nonaromatisable androgen dihydrotestosterone (DHT) significantly stimulates MC3T3preosteoblast differentiation with no effect on cell growth in this in-vitro study. This effect of DHT was accompanied by increased Wnt signalling in the same cells.
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34548515482
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Takai H, Nakayama Y, Kim DS, et al. Androgen receptor stimulates bone sialoprotein (BSP) gene transcription via cAMP response element and activator protein 1/glucocorticoid response elements. J Cell Biochem 2007; 102:240-251. Bone sialoprotein (BSP) is an early marker of osteoblast differentiation. This study demonstrates that AR stimulates BSP gene transcription by targeting the CRE and AP1/GRE elements in the promoter of the rat BSP gene.
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Takai H, Nakayama Y, Kim DS, et al. Androgen receptor stimulates bone sialoprotein (BSP) gene transcription via cAMP response element and activator protein 1/glucocorticoid response elements. J Cell Biochem 2007; 102:240-251. Bone sialoprotein (BSP) is an early marker of osteoblast differentiation. This study demonstrates that AR stimulates BSP gene transcription by targeting the CRE and AP1/GRE elements in the promoter of the rat BSP gene.
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19
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0035016058
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The effects of oestrogens on linear bone growth
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Juul A. The effects of oestrogens on linear bone growth. Hum Reprod Update 2001; 7:303-313.
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(2001)
Hum Reprod Update
, vol.7
, pp. 303-313
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Juul, A.1
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20
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33845932363
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Venken K, Movérare-Skrtic S, Kopchick JJ, et al. Impact of androgens, growth hormone, and IGF-I on bone and muscle in male mice during puberty. J Bone Miner Res 2007; 22:72-82. The aim of the study was to investigate androgen action on bone and muscle during puberty in the presence and absence of a functional GH/IGF-I axis. Androgens stimulate trabecular and cortical bone modelling and increase muscle weight independently from either systemic or local IGF-I production.
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Venken K, Movérare-Skrtic S, Kopchick JJ, et al. Impact of androgens, growth hormone, and IGF-I on bone and muscle in male mice during puberty. J Bone Miner Res 2007; 22:72-82. The aim of the study was to investigate androgen action on bone and muscle during puberty in the presence and absence of a functional GH/IGF-I axis. Androgens stimulate trabecular and cortical bone modelling and increase muscle weight independently from either systemic or local IGF-I production.
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21
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34250722058
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Wang X, Rundle CH, Wergedal JE, et al. Loss of sex-specific difference in femoral bone parameters in male leptin knockout mice. Calcif Tissue Int 2007; 80:374-382. Sex-dependent differences were identified in the femoral bone parameters of male and female ob/ob (leptin knockout) mice compared with their wild-type background strain. Sexual dimorphism of skeletal size was observed in wildtype but not in leptin knockout mice. The authors suggest that this may be related to differences in androgen signalling. However, lean body mass also showed no gender difference in leptin knockout mice in contrast with wildtype.
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Wang X, Rundle CH, Wergedal JE, et al. Loss of sex-specific difference in femoral bone parameters in male leptin knockout mice. Calcif Tissue Int 2007; 80:374-382. Sex-dependent differences were identified in the femoral bone parameters of male and female ob/ob (leptin knockout) mice compared with their wild-type background strain. Sexual dimorphism of skeletal size was observed in wildtype but not in leptin knockout mice. The authors suggest that this may be related to differences in androgen signalling. However, lean body mass also showed no gender difference in leptin knockout mice in contrast with wildtype.
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34548274444
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Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts
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The results of this elegant study support a model in which estrogen regulates the life span of mature osteoclasts through the induction of the Fas/FasL system, thereby providing an explanation for the osteoprotective function of estrogen as well as SERMs
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Nakamura T, Matsumoto T, Sato S, et al. Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts. Cell 2007; 130:811-823. The results of this elegant study support a model in which estrogen regulates the life span of mature osteoclasts through the induction of the Fas/FasL system, thereby providing an explanation for the osteoprotective function of estrogen as well as SERMs.
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(2007)
Cell
, vol.130
, pp. 811-823
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Nakamura, T.1
Matsumoto, T.2
Sato, S.3
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24
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33846007358
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Genetic evidence of androgen receptor function in osteoclasts: Generation and characterization of osteoclast-specific androgen receptor knockout mice
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Nakamura T, Watanabe T, Nakamichi Y, et al. Genetic evidence of androgen receptor function in osteoclasts: generation and characterization of osteoclast-specific androgen receptor knockout mice. J Bone Miner Res 2004; 19 (Suppl 1):S3.
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(2004)
J Bone Miner Res
, vol.19
, Issue.SUPPL. 1
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Nakamura, T.1
Watanabe, T.2
Nakamichi, Y.3
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25
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33646036678
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FSH directly regulates bone mass
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Sun L, Peng Y, Sharrow A, et al. FSH directly regulates bone mass. Cell 2006; 125:247-260.
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(2006)
Cell
, vol.125
, pp. 247-260
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Sun, L.1
Peng, Y.2
Sharrow, A.3
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26
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34250824919
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Altered ovarian function affects skeletal homeostasis independent of the action of follicle-stimulating hormone
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Gao J, Tiwari-Pandey R, Samadfan R, et al. Altered ovarian function affects skeletal homeostasis independent of the action of follicle-stimulating hormone. Endocrinology 2007; 148:2613-2621.
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(2007)
Endocrinology
, vol.148
, pp. 2613-2621
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Gao, J.1
Tiwari-Pandey, R.2
Samadfan, R.3
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27
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34250887411
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Hypogonadal bone loss: Sex steroids or gonadotropins?
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Williams GR. Hypogonadal bone loss: sex steroids or gonadotropins? Endocrinology 2007; 148:2610-2612.
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(2007)
Endocrinology
, vol.148
, pp. 2610-2612
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Williams, G.R.1
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Sex steroids, not FSH, influence bone mass
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author reply 1080-1081
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Seibel MJ, Dunstan C, Zhou H, et al. Sex steroids, not FSH, influence bone mass. Cell 2006; 127:1079; author reply 1080-1081.
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(2006)
Cell
, vol.127
, pp. 1079
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Seibel, M.J.1
Dunstan, C.2
Zhou, H.3
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Notini AJ, McManus JF, Moore A, et al. Osteoblast deletion of exon 3 of the androgen receptor gene results in trabecular bone loss in adult male mice. J Bone Miner Res 2007; 22:347-356. The aim of this study was to investigate the role of androgens acting through the classical androgen receptor (AR)-signalling pathways (i.e., DNA-binding dependent pathways) in osteoblasts using male mice in which exon 3 of the AR gene was deleted specifically in mature osteoblasts. These mice had decreased trabecular bone however only at older age associated with a decrease in trabecular number, suggesting that androgens may act - at least partly - directly on osteoblasts to maintain trabecular bone.
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Notini AJ, McManus JF, Moore A, et al. Osteoblast deletion of exon 3 of the androgen receptor gene results in trabecular bone loss in adult male mice. J Bone Miner Res 2007; 22:347-356. The aim of this study was to investigate the role of androgens acting through the classical androgen receptor (AR)-signalling pathways (i.e., DNA-binding dependent pathways) in osteoblasts using male mice in which exon 3 of the AR gene was deleted specifically in mature osteoblasts. These mice had decreased trabecular bone volume however only at older age associated with a decrease in trabecular number, suggesting that androgens may act - at least partly - directly on osteoblasts to maintain trabecular bone.
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Miner JN, Chang W, Chapman MS, et al. An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate. Endocrinology 2007; 148:363-373. Animal and in-vitro data obtained with an orally available, nonaromatizable androgen demonstrate the important role of the AR and androgens in mediating a number of beneficial effects in bone, muscle and sexual function independent from the conversion of androgens into estrogenic ligands. These results suggest that orally active, nonsteroidal selective androgen receptor modulators may be useful therapeutics for enhancing muscle, bone and sexual function.
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Miner JN, Chang W, Chapman MS, et al. An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate. Endocrinology 2007; 148:363-373. Animal and in-vitro data obtained with an orally available, nonaromatizable androgen demonstrate the important role of the AR and androgens in mediating a number of beneficial effects in bone, muscle and sexual function independent from the conversion of androgens into estrogenic ligands. These results suggest that orally active, nonsteroidal selective androgen receptor modulators may be useful therapeutics for enhancing muscle, bone and sexual function.
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22544467523
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Discovery and therapeutic promise of selective androgen receptor modulators
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Chen J, Kim J, Dalton JT. Discovery and therapeutic promise of selective androgen receptor modulators. Mol Interv 2005; 5:173-188.
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(2005)
Mol Interv
, vol.5
, pp. 173-188
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Chen, J.1
Kim, J.2
Dalton, J.T.3
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33
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26844496083
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Selective androgen receptor modulator treatment improves muscle strength and body composition and prevents bone loss in orchidectomized rats
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Gao W, Reiser P, Coss C, et al. Selective androgen receptor modulator treatment improves muscle strength and body composition and prevents bone loss in orchidectomized rats. Endocrinology 2005; 146:4887-4897.
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(2005)
Endocrinology
, vol.146
, pp. 4887-4897
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Gao, W.1
Reiser, P.2
Coss, C.3
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Selective androgen receptor modulator (SARM) treatment prevents bone loss and reduces body fat in ovariectomized rats
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Kearbey JD, Gao W, Narayanan R, et al. Selective androgen receptor modulator (SARM) treatment prevents bone loss and reduces body fat in ovariectomized rats. Pharm Res 2007; 24:328-335.
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(2007)
Pharm Res
, vol.24
, pp. 328-335
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Kearbey, J.D.1
Gao, W.2
Narayanan, R.3
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Borst SE, Conover CF, Carter CS, et al. Anabolic effects of testosterone are preserved during inhibition of 5alpha-reductase. Am J Physiol Endocrinol Metab 2007; 293:E507-E514. In contrast to the prostate effects of testosterone, the effects on muscle, bone and haemoglobin concentration were not blocked by the selective 5 alpha reductase inhibitor MK-434 in an orchidectomized rat model. The effects of testosterone on muscle and bone can therefore be separated from the prostate effects and provides a testable strategy for combating sarcopenia and osteopenia in older hypogonadal men.
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Borst SE, Conover CF, Carter CS, et al. Anabolic effects of testosterone are preserved during inhibition of 5alpha-reductase. Am J Physiol Endocrinol Metab 2007; 293:E507-E514. In contrast to the prostate effects of testosterone, the effects on muscle, bone and haemoglobin concentration were not blocked by the selective 5 alpha reductase inhibitor MK-434 in an orchidectomized rat model. The effects of testosterone on muscle and bone can therefore be separated from the prostate effects and provides a testable strategy for combating sarcopenia and osteopenia in older hypogonadal men.
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1442278883
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Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone
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Amory JK, Watts N, Easley K, et al. Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. J Clin Endocrinol Metab 2004; 89:503-510.
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(2004)
J Clin Endocrinol Metab
, vol.89
, pp. 503-510
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Amory, J.K.1
Watts, N.2
Easley, K.3
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Bone mineral density in the complete androgen insensitivity and 5alpha-reductase-2 deficiency syndromes
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Sobel V, Schwartz B, Zhu Y, et al. Bone mineral density in the complete androgen insensitivity and 5alpha-reductase-2 deficiency syndromes. J Clin Endocrinol Metab 2006; 91:3017-3023.
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(2006)
J Clin Endocrinol Metab
, vol.91
, pp. 3017-3023
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Sobel, V.1
Schwartz, B.2
Zhu, Y.3
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Bjornerem A, Ahmed LA, Joakimsen RM, et al. A prospective study of sex steroids, sex hormone-binding globulin, and nonvertebral fractures in women and men: the Tromso Study. Eur J Endocrinol 2007; 157:119-125. In this prospective cohort study, the combination of body mass density (BMD) and sex hormone binding globulin (SHBG) was no better predictor of fracture risk in both sexes than BMD alone. Sex steroids were not associated with fracture risk. Authors conclude that measurements of sex steroids or SHBG are therefore unlikely to assist in decision-making regarding fracture risk susceptibility.
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Bjornerem A, Ahmed LA, Joakimsen RM, et al. A prospective study of sex steroids, sex hormone-binding globulin, and nonvertebral fractures in women and men: the Tromso Study. Eur J Endocrinol 2007; 157:119-125. In this prospective cohort study, the combination of body mass density (BMD) and sex hormone binding globulin (SHBG) was no better predictor of fracture risk in both sexes than BMD alone. Sex steroids were not associated with fracture risk. Authors conclude that measurements of sex steroids or SHBG are therefore unlikely to assist in decision-making regarding fracture risk susceptibility.
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Almeida M, Han L, Martin-Millan M, et al. Skeletal involution by age-associated oxidative stress and its acceleration by loss of sex steroids. J Biol Chem 2007; 282:27285-27297. Both female and male mice show progressive age-related loss of BMD and strength. Such loss is associated with a decreased rate of osteoblast and osteoclast numbers and decreased bone formation rate; as well as increased osteoblast and osteocyte apoptosis, increased reactive oxygen species levels and decreased defence against oxidative stress. Exactly the same changes in oxidative stress were acutely reproduced by gonadectomy in adult females or males and reversed by estrogens or androgens in vivo as well as in vitro. Loss of estrogens or androgens may therefore accelerate the effects of ageing on bone by decreasing defence against oxidative stress
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Almeida M, Han L, Martin-Millan M, et al. Skeletal involution by age-associated oxidative stress and its acceleration by loss of sex steroids. J Biol Chem 2007; 282:27285-27297. Both female and male mice show progressive age-related loss of BMD and strength. Such loss is associated with a decreased rate of osteoblast and osteoclast numbers and decreased bone formation rate; as well as increased osteoblast and osteocyte apoptosis, increased reactive oxygen species levels and decreased defence against oxidative stress. Exactly the same changes in oxidative stress were acutely reproduced by gonadectomy in adult females or males and reversed by estrogens or androgens in vivo as well as in vitro. Loss of estrogens or androgens may therefore accelerate the effects of ageing on bone by decreasing defence against oxidative stress.
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