Delemarre-Van de Waal, H.A.

Estrogen receptor-alpha gene polymorphisms and body composition in children and adolescents (Article)

2011-08-01T00:00:00Z

Background/Aims: Gender differences in body composition are largely explained by differences in sex hormones, such as estrogens. Associations between 2 polymorphisms in the estrogen receptor-α gene (ESR1) and body composition in children and adolescents were investigated. Methods: Two comparable Dutch cohorts with a generational difference of about 20 years were investigated. The first consisted of 350 subjects (184 girls) and the second of 316 subjects (155 girls). Associations between height, weight, BMI, fat mass (FM) and fat-free mass and two polymorphisms in the ESR1 gene were investigated. Results: In girls in the recent cohort, the PvuII-XbaI haplotype 2 polymorphism in the ESR1 gene was associated with a lower body weight, BMI, and FM. These associations were not observed in the older cohort. The younger cohort had a significantly higher total FM, body weight and BMI compared to the older cohort. Conclusion: Because the associations between the PvuII-XbaI haplotype 2 polymorphism and body FM in girls were only found in the recent cohort, but not in a comparable, generally leaner cohort from an older generation, it is suggested that non-carriers of this polymorphism are likely to be more vulnerable to fat accumulation in today's obesity promoting environment, than carriers. Copyright

High-dose GH treatment limited to the prepubertal period in young children with idiopathic short stature does not increase adult height (Article)

2010-04-01T00:00:00Z

Objective: To assess the long-term effect of prepubertal high-dose GH treatment on growth in children with idiopathic short stature (ISS). Design and methods: Forty children with no signs of puberty, age at start 4-8 years (girls) or 4-10 years (boys), height SDS <2-.0 SDS, and birth length >-2.0 SDS, were randomly allocated to receive GH at a dose of 2 mg/m2per day (equivalent to 75 μg/kg per day at start and 64 μg/kg per day at stop) until the onset of puberty for at least 2 years (preceded by two 3-month periods of treatment with low or intermediate doses of GH separated by two washout periods of 3 months) or no treatment. In 28 cases, adult height (AH) was assessed at a mean (S.D.) age of 20.4 (2.3) years. Results: GH-treated children (mean treatment period on high-dose GH 2.3 years (range 1.2-5.0 years)) showed an increased mean height SDS at discontinuation of the treatment compared with the controls (-1.3 (0.8) SDS versus -2.6 (0.8) SDS respectively). However, bone maturation was significantly accelerated in the GH-treated group compared with the controls (1.6 (0.4) versus 1.0 (0.2) years per year, respectively), and pubertal onset tended to advance. After an untreated interval of 3-12 years, AH was -2.1 (0.7) and -1.9 (0.6) in the GH-treated and control groups respectively. Age was a positive predictor of adult height gain. Conclusion: High-dose GH treatment restricted to the prepubertal period in young ISS children augments height gain during treatment, but accelerates bone maturation, resulting in a similar adult height compared with the untreated controls.

Glucocorticoid receptor gene polymorphism is less frequent in children born small for gestational age without catch-up growth (Article)

2009-02-01T00:00:00Z

Background/Aims: Glucocorticoids are important regulators of many processes involved in embryonal growth and development and fat and glucose metabolism. Glucocorticoids exert their effect through the glucocorticoid receptor (GR). The aim of this study was to investigate possible associations between 4 well-known GR gene haplotypes and size at birth. Methods: We investigated associations between GR haplotypes and size at birth in a Dutch reference cohort. This reference cohort consisted of 222 young healthy Caucasian subjects. Associations between size at birth and glucocorticoid receptor gene haplotypes were tested. Furthermore, we investigated a group of 119 children born small for gestational age (SGA), without catch-up growth. Prevalence of the different GR haplotypes was compared between the SGA group and the reference cohort. Results: No associations were found between any of the GR haplotypes and birth weight or birth length in the reference group. The prevalence of GR haplotype 2 (Bcl1) was significantly lower in the SGA group compared to controls. Conclusion: Genetic variance in the GR seems not to be associated with intrauterine growth in the general population. However, GR haplotype might play a role in growth of children born SGA, reflected by the decreased prevalence of GR haplotype 2 (Bcl1) in this group. Copyright

Increased blood pressure variability in aging rats after intrauterine growth restriction [2] (Article)

2007-11-01T00:00:00Z

Final height outcome after three years of growth hormone and gonadotropin-releasing hormone agonist treatment in short adolescents with relatively early puberty (Article)

2007-04-01T00:00:00Z

Objective: Our objective was to assess final height (FH) and adverse effects of combined GH and GnRH agonist (GnRHa) treatment in short adolescents born small for gestational age or with normal birth size (idiopathic short stature). Design and Patients: Thirty-two adolescents with Tanner stage 2-3, age and bone age (BA) less than 12 yr for girls or less than 13 yr for boys, height SD score (SDS) less than -2.0 SDS or between -1.0 and -2.0 SDS plus a predicted adult height (PAH0) less than -2.0 SDS were randomly allocated to receive GH plus GnRHa (n = 17) or no treatment (n = 15) for 3 yr. FH was assessed at the age of 18 yr or older in girls or 19 yr or older in boys. Results: FH was not different between treatment and control groups. Treated children had a larger height gain (FH - PAH0) than controls: 4.4 (4.9) and -0.5 (6.4) cm, respectively (P < 0.05). FH was higher than PAH0in 76 and 60% of treated and control subjects, respectively. During follow-up, 50% of the predicted height gain at treatment withdrawal was lost, resulting in a mean gain of 4.9 cm (range, -4.0 to 12.3 cm) compared with controls. Treatment did not affect body mass index or hip bone mineral density. Mean lumbar spine bone mineral density and bone mineral apparent density tended to be lower in treated boys, albeit statistically not significant. Conclusion: Given the expensive and intensive treatment regimen, its modest height gain results, and the possible adverse effect on peak bone mineralization in males, GH plus GnRHa cannot be considered routine treatment for children with idiopathic short stature or persistent short stature after being born small for gestational age. Copyright

Weekend versus working day: Differences in telemetric blood pressure in male Wistar rats (Article)

2007-01-01T00:00:00Z

Blood pressure (BP) is a frequently monitored parameter in research. Various methods are used to obtain BP values in animal models, but telemetry is the method of choice because it allows for continuous monitoring in conscious and freely moving animals. However, factors due to the animal facility, like activities and sound, can still influence measurements. We, therefore, retrospectively compared BP values in adult male Wistar rats during working hours with values from non-working days. Telemetry devices were implanted according to standard protocol. Values were obtained at the age of 6 and 12 months during working hours (Friday 10:00-16:00 h, lights on 06:00-18:00 h) and compared with data from the average of Saturday 10:00-16:00 h and Sunday 10:00-16:00 h, representing non-working days. Data were available from 12 and 7 rats at 6 months and 12 months of age respectively. Relative differences in heart rate, spontaneous locomotor activity, systolic and diastolic BP were 2.2% (P<0.001), 32.9% (P<0.05), 3.2% (P<0.05) and3.7% (P<0.05), respectively, with no differences between the age groups. We have shown a significant and important difference between BP values obtained during working hours and non-working days using telemetry in adult male Wistar rats. This phenomenon has implications for the interpretation of BP measurements in animals.