Dihydrotestosterone Prevents Glucocorticoid-Negative Effects on Fetal Rat Metatarsal Bone in vitro

Picherit, Christel; Coxam, Véronique; Oudadesse, H.; Martini, Brigitte; Gaumet, N.; Davicco, M J; Lebecque, Patrice; Miller, Scott C.; Irrigaray, Jean Léon; Barlet, J. P.

doi:10.1159/000014214

Cited by 7 publications

(4 citation statements)

References 54 publications

(56 reference statements)

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“…The reduction in length of the mineralization zone with Dex was consistent with metatarsals treated with hydrocortisone (27). However, the absence of an increase in the length of this zone after IGF-I is at variance to others who have demonstrated an increase in mineralization zone length with IGF-I in a rat metatarsal model system (19).…”

Section: Discussionsupporting

confidence: 72%

Insulin-Like Growth Factor-I Augments Chondrocyte Hypertrophy and Reverses Glucocorticoid-Mediated Growth Retardation in Fetal Mice Metatarsal Cultures

et al. 2004

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The study aims were to improve our understanding of the mechanisms of glucocorticoid-induced growth retardation at the growth plate and determine whether IGF-I could ameliorate the effects. Fetal mouse metatarsals were cultured for up to 10 d with dexamethasone (Dex; 10(-6) m) and/or IGF-I and GH (both at 100 ng/ml). Both continuous and alternate-day Dex treatment inhibited bone growth to a similar degree, whereas IGF-I alone or together with Dex caused an increase in bone growth. GH had no effects. These observations may be explained at the cellular level; cell proliferation within the growing bone was decreased by Dex and increased by IGF-I and these effects were more marked in the cells of the perichondrium than those in the growth plate. However, the most prominent observation was noted in the hypertrophic zone where all treatments containing IGF-I significantly increased (3-fold) the length of this zone, whereas Dex alone had no significant effect. In conclusion, Dex impaired longitudinal growth by inhibiting chondrocyte proliferation, whereas IGF-I stimulated chondrocyte hypertrophy and reversed the growth-inhibitory Dex effects. However, the IGF-I-mediated improvement in growth was at the expense of altering the balance between proliferating and hypertrophic chondrocytes within the metatarsal.

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Section: Discussionsupporting

confidence: 72%

Insulin-Like Growth Factor-I Augments Chondrocyte Hypertrophy and Reverses Glucocorticoid-Mediated Growth Retardation in Fetal Mice Metatarsal Cultures

et al. 2004

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“…In line with our findings, AR stimulation was previously demonstrated not to affect the length of cultured fetal rat metatarsal bones [27]. Nevertheless, androgen responsiveness might differ between species, which is supported by the observations that dihydrotestosterone increases DNA synthesis in fetal human epiphyseal chondrocytes [28], and that testosterone stimulates the growth of mouse cartilage [29, 30].…”

Section: Discussionsupporting

confidence: 89%

“…Nevertheless, androgen responsiveness might differ between species, which is supported by the observations that dihydrotestosterone increases DNA synthesis in fetal human epiphyseal chondrocytes [28], and that testosterone stimulates the growth of mouse cartilage [29, 30]. Nevertheless, in cultured fetal rat metatarsal bones, dihydrotestosterone has been demonstrated to prevent the negative effects of glucocorticoids [27], raising the possibility that rat cartilage might be androgen-responsive anyway. Our finding that oxandrolone and testosterone, despite not affecting longitudinal bone growth, clearly inhibited chondrocyte mineralization, supports that the fetal rat cartilage employed in our study is indeed capable of responding to androgens.…”

Section: Discussionmentioning

confidence: 99%

Androgen Receptor Modulation Does Not Affect Longitudinal Growth of Cultured Fetal Rat Metatarsal Bones

Chagin

Vannesjö²,

Sävendahl³

2009

Horm Res Paediatr

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Background: Systemic administration of the nonaromatizable androgen oxandrolone stimulates growth in girls with Turner syndrome and boys with a constitutional delay of growth and puberty. It is unknown if oxandrolone acts locally at the growth plate level to stimulate longitudinal bone growth. Methods: Metatarsal bones from female and male rat fetuses (day E20) were cultured for 14 days in the presence of oxandrolone, testosterone or the androgen receptor (AR) antagonist flutamide with/without insulin-like growth-factor-I (IGF-I) or charcoal-treated serum. Results: The AR was found to be expressed in both male and female fetal rat metatarsal bones. Neither oxandrolone nor testosterone had any effect on metatarsal bone growth when tested at a wide concentration range (1 nM to 10 μM), not even in the presence of IGF-I (100 ng/ml) or charcoal-treated serum (10%). Bone growth was also unaffected when the AR was blocked by flutamide. Control experiments confirmed that metatarsal bone growth was significantly stimulated by IGF-I (p < 0.001). Conclusion: Modulation of AR activity in the fetal rat growth plate does not affect linear bone growth. Extrapolating from these in vitro data, it could be speculated that oxandrolone stimulates longitudinal bone growth in treated children by acting indirectly rather than directly through AR activation in growth plate chondrocytes.

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“…One of the best-known isoflavones i.e. genistein is absorbed in the small intestine (Picherit et al, 2000), can be detected in plasma and serum after oral administration (Rowland et al, 2003), and crosses the blood-brain barrier (Tsai, 2005). Genistein has a structure similar to 17β-oestradiol, and it can bind to the oestrogen receptors (Lephart et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Genistein inhibits aggregation of exogenous amyloid-beta1–40 and alleviates astrogliosis in the hippocampus of rats

et al. 2012

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We addressed the question of whether injection of Aβ in the rat brain is associated with pathology in the hippocampus, and if genistein has any protective effect against the neuronal damage caused by Aβ 1-40 . Genistein is a plant-derived compound with a structure similar to that of the female sex hormone oestrogen and it was recently shown that pretreatment with a single dose of genistein ameliorated learning and memory deficits in an amyloid beta (Aβ) 1-40 rat model of Alzheimer's disease. Here, we report that injection of the amyloid peptide into the hippocampus of rats led to formation of Aβ 1-40 positive aggregates close to the lateral blade of the dentate gyrus (DGlb). We also observed the following in the hippocampus: extensive cell death in the DGlb (P < 0.0001), CA1 (P = 0.03), and CA3 (P = 0.002); an increased number of iNOS-expressing cells (P = 0.01) and gliosis. Genistein given to rats by gavage one hour before Key words: amyloid-beta, Alzheimer's disease, genistein, neuronal degeneration 1 1 Abbreviations: AD, Alzheimer's disease; iNOS, inducible nitric oxide synthase; nNOS, neuronal nitric oxide synthase; CA1, cornu ammonis 1; CA2, cornu ammonis 2; CA3, cornu ammonis 3; Aβ, amyloid beta; DGlb, lateral blade of dentate gyrus; DGmb, medial blade of dentate gyrus; GFAP, glial fibrillary acidic protein; CC, corpus callosum; MAP, mitogenactivated protein; NFĸB, nuclear factor kappa B; MnSOD, manganese superoxide dismutase; APP, amyloid precursor protein; CrEL, Cremophor EL

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Dihydrotestosterone Prevents Glucocorticoid-Negative Effects on Fetal Rat Metatarsal Bone in vitro

Cited by 7 publications

References 54 publications

Insulin-Like Growth Factor-I Augments Chondrocyte Hypertrophy and Reverses Glucocorticoid-Mediated Growth Retardation in Fetal Mice Metatarsal Cultures

Insulin-Like Growth Factor-I Augments Chondrocyte Hypertrophy and Reverses Glucocorticoid-Mediated Growth Retardation in Fetal Mice Metatarsal Cultures

Androgen Receptor Modulation Does Not Affect Longitudinal Growth of Cultured Fetal Rat Metatarsal Bones

Genistein inhibits aggregation of exogenous amyloid-beta1–40 and alleviates astrogliosis in the hippocampus of rats

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