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

Chagin, Andrei S.; Vannesjö, Johanna; Sävendahl, Lars

doi:10.1159/000201111

Cited by 9 publications

(11 citation statements)

References 70 publications

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“…The mechanism by which Ox influences growth is unclear. A positive effect on the growth plate as well as effects via other growth factors such as IGF1 have been suggested (25,26). Data of our original study and the US study point toward a dose-dependent effect of Ox on bone maturation (8,12).…”

Section: Discussionmentioning

confidence: 65%

Long-term effects of previous oxandrolone treatment in adult women with Turner syndrome

Freriks

Sas

Traas

et al. 2013

European Journal of Endocrinology

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Objective: Short stature is a prominent feature of Turner syndrome (TS), which is partially overcome by GH treatment. We have previously reported the results of a trial on the effect of oxandrolone (Ox) in girls with TS. Ox in a dose of 0.03 mg/kg per day (Ox 0.03) significantly increased adult height gain, whereas Ox mg/kg per day (0.06) did not, at the cost of deceleration of breast development and mild virilization. The aim of this follow-up study in adult participants of the pediatric trial was to investigate the long-term effects of previous Ox treatment. Design and methods: During the previous randomized controlled trial, 133 girls were treated with GH combined with placebo (Pl), Ox 0.03, or Ox 0.06 from 8 years of age and estrogen from 12 years. Sixtyeight women (Pl, nZ23; Ox 0.03, nZ27; and Ox 0.06, nZ18) participated in the double-blind followup study (mean age, 24.0 years; mean time since stopping GH, 8.7 years; and mean time of Ox/Pl use, 4.9 years). We assessed height, body proportions, breast size, virilization, and body composition. Results: Height gain (final minus predicted adult height) was maintained at follow-up (Ox 0.03 10.2 G4.9 cm, Ox 0.06 9.7G4.4 cm vs Pl 8.0G4.6 cm). Breast size, Tanner breast stage, and body composition were not different between groups. Ox-treated women reported more subjective virilization and had a lower voice frequency. Conclusion: Ox 0.03 mg/kg per day has a beneficial effect on adult height gain in TS patients. Despite previously reported deceleration of breast development during Ox 0.03 treatment, adult breast size is not affected. Mild virilization persists in only a small minority of patients. The long-term evaluation indicates that Ox 0.03 treatment is effective and safe.European Journal of Endocrinology 168 91-99

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Section: Discussionmentioning

confidence: 65%

Long-term effects of previous oxandrolone treatment in adult women with Turner syndrome

Freriks

Sas

Traas

et al. 2013

European Journal of Endocrinology

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“…Based on our previous studies on short-term cultures of fetal rat metatarsal bones, we believe that bones cultured in DMEM/F12 medium (Chagin et al 2006 grow better than those cultured in MEM (Mancilla et al 1998, Martensson et al 2004, Zaman et al 2007 or alpha MEM (Chagin et al 2009) media. However, a direct formal comparison has never been made before.…”

Section: Establishment Of Long-term Cultures Of Fetal and Postnatal Rmentioning

confidence: 99%

“…Hypertropic chondrocytes were defined by a height of more than 7 mm (Tivesten et al 2004). The size of hypertropic chondrocytes was averaged by measuring 25 hypertropic chondrocytes per distal growth plate in the hypertropic zone between the third and seventh cell layers (counted from the metaphyseal side; Chagin et al 2009). Measurements were performed using the Image-ProPlus image analysis software (Media Cybernetic).…”

Section: Quantitative Histologymentioning

confidence: 99%

Catch-up growth after dexamethasone withdrawal occurs in cultured postnatal rat metatarsal bones

Chagin¹,

Karimian²,

Sundström³

et al. 2009

Journal of Endocrinology

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Children exposed to systemic glucocorticoids often exhibit growth retardation and after the cessation of therapy catch-up growth occurs in many, but not all patients. The developmental regulation and underlying cellular mechanisms of catch-up growth are not fully understood. To clarify this issue, we established an in vitro model of catch-up growth. Here we present a protocol for the long-term culture (up to 160 days) of fetal (E20) as well as postnatal (P8) rat metatarsal bones which allowed us to characterize ex vivo the phenomenon of catch-up growth without any influence by systemic factors. The relevance of the model was confirmed by the demonstration that the growth of fetal and postnatal bones were stimulated by IGF1 (100 ng/ml) and inhibited by dexamethasone (Dexa; 1 mM). We found that the capacity to undergo catch-up growth was restricted to postnatal bones. Catch-up growth occurred after postnatal bones had been exposed to Dexa for 7 or 12 days but not after a more prolonged exposure (19 days). Incomplete catch-up growth resulted in compromised bone length when assessed at the end of the 4-month period of culture. While exposure to Dexa was associated with decreased chondrocyte proliferation and differentiation, catchup growth was only associated with increased cell proliferation. We conclude that the phenomenon of catch-up growth after Dexa treatment is intrinsic to the growth plate and primarily mediated by an upregulation of chondrocyte proliferation.

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“…It could be due to a systemic effect via the GH-insulin like growth factor 1 (IGF-1) system or a direct action on the androgen receptor in growth plate cartilage. A direct effect on chondrocytes is less likely as Ox had no effect on linear growth in a rat metatarsal organ culture model [33]. The possibility that the effect could be GH-mediated deserves consideration.…”

Section: Discussionmentioning

confidence: 99%

Effect of Oxandrolone and Timing of Oral Ethinylestradiol Initiation on Pubertal Progression, Height Velocity and Bone Maturation in the UK Turner Study

et al. 2014

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Background: A UK study showed final height in Turner syndrome (TS) girls receiving growth hormone is affected by age at pubertal induction and oxandrolone (Ox). Using data from that study, we analysed the effect of timing of oral ethinylestradiol (EE₂) and Ox on height velocity (HV), bone maturation and pubertal progression, and compared growth response in EE₂-treated versus spontaneous puberty. Methods: Analysis of HV, bone age and pubertal stage in 92 TS girls (7-13 years) randomised to Ox (0.05 mg/kg/day; max: 2.5 mg/day) or placebo from 9 years, and EE₂ (year 1: 2 µg/day; year 2: 4 µg/day; year 3: 6/8/10 µg/day × 4 months) or placebo at 12 years with EE₂ at 14 years. Girls enrolled at >12.25 years received EE₂ at 14 years (‘late group'). Results: Fifty-six girls were randomised to EE₂ at 12 years (n = 28, 11 Ox) or 14 years (n = 28, 13 Ox); there were 19 girls in the late group (9 Ox) and 17 girls with spontaneous puberty (10 Ox). Girls receiving EE₂ at 12 versus 14 years had faster bone maturation, but neither group showed acceleration. Ox increased HV without altering bone maturation or pubertal progression. Girls with spontaneous puberty had greater pubertal growth (mean PHV 8.5 cm/year; p < 0.001) and height gain (p < 0.001) than EE₂-treated girls despite similar mean enrolment height SD and dysmorphology scores. Conclusion: Pubertal induction with EE₂ does not replicate the acceleration observed in unaffected girls or TS girls with spontaneous puberty.

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

Cited by 9 publications

References 70 publications

Long-term effects of previous oxandrolone treatment in adult women with Turner syndrome

Long-term effects of previous oxandrolone treatment in adult women with Turner syndrome

Catch-up growth after dexamethasone withdrawal occurs in cultured postnatal rat metatarsal bones

Effect of Oxandrolone and Timing of Oral Ethinylestradiol Initiation on Pubertal Progression, Height Velocity and Bone Maturation in the UK Turner Study

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