| 1. |
- Ankarberg-Lindgren, Carina, 1963, et al.
(författare)
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Leptin levels show diurnal variation throughout puberty in healthy children, and follow a gender-specific pattern
- 2001
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Ingår i: Eur J Endocrinol. ; 145:1, s. 43-51
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the levels and diurnal rhythm of serum leptin in healthy children, and to investigate the association between leptin levels and sex steroids. METHODS: Four girls and four boys, all healthy volunteers, were followed longitudinally throughout puberty. Their chronological ages ranged from 8.7 to 19.5 years, and body composition, expressed as weight-for-height standard deviation scores (SDS), ranged between -1.7 and +2.4. Serum leptin, oestradiol and testosterone concentrations were measured by radioimmunoassay at 1000, 1400, 1800, 2200, 0200 and 0600 h. RESULTS: In all girls and boys, both prepubertally and during pubertal development, serum leptin levels increased during the night, with no difference in relative peak amplitude. In boys, the leptin concentrations increased until the initiation of puberty and then declined, whereas in girls, the concentrations increased throughout puberty. The inter-individual variation in mean leptin levels among girls decreased to 11% at the time of menarche. A positive correlation was found for both oestradiol and testosterone versus leptin in girls throughout puberty (r=0.64 and r=0.71 respectively, P<0.001). A negative correlation was found between leptin and testosterone in boys in mid- and late puberty (r=-0.66, P<0.01). No correlation was found between oestradiol and leptin in boys or between testosterone and leptin in pre- and early pubertal boys. CONCLUSION: Serum leptin concentrations show diurnal variation throughout pubertal development in both girls and boys. The changes in leptin levels during puberty follow a gender-specific pattern, probably due to an influence of sex steroids on leptin production.
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| 2. |
- Ankarberg-Lindgren, Carina, 1963, et al.
(författare)
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Nocturnal application of transdermal estradiol patches produces levels of estradiol that mimic those seen at the onset of spontaneous puberty in girls.
- 2001
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Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X .- 1945-7197. ; 86:7, s. 3039-44
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Tidskriftsartikel (refereegranskat)abstract
- The objective of pubertal induction in children with hypogonadism is to mimic spontaneous puberty in terms of physical and psychological development. In a clinical observation study, we induced puberty in 15 girls with hyper- or hypogonadotropic hypogonadism using low doses of transdermal estradiol patches attached only during the night and compared the estradiol concentrations obtained with those in healthy girls. Pubertal induction was started between the ages of 12.3 and 18.1 yr. A transdermal matrix patch of 17beta-estradiol (25 microg/24 h; Evorel, Janssen Pharmaceuticals-Cilag) was cut into pieces corresponding to 3.1, 4.2, or 6.2 microg/24 h initially and attached to the buttock. After 4-14 months, the dose was increased gradually. Serum 17beta-estradiol concentrations were measured every 2 h by RIA (detection limit, 6.0 pmol/L; 1.6 pg/mL). The results show that it is possible to mimic the spontaneous levels as well as the diurnal pattern of serum 17beta-estradiol in early puberty, by cutting a transdermal 17beta-estradiol matrix patch and attaching a part of it, corresponding to 0.08-0.12 microg estradiol/kg BW, to the buttock nocturnally. In most of the girls, breast development occurred within 3-6 months of the start of treatment.
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| 3. |
- Bjarnason, Ragnar, 1959, et al.
(författare)
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Cartilage oligomeric matrix protein increases in serum after the start of growth hormone treatment in prepubertal children
- 2004
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 89:10, s. 5156-60
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Tidskriftsartikel (refereegranskat)abstract
- Both GH and IGF-I stimulate bone growth, but the molecular mechanisms mediating their effects on the growth plate are not fully understood. We measured gene expression by microarray analysis in primary cultured human chondrocytes treated with either GH or IGF-I. One of the genes found to be up-regulated by both GH and IGF-I was that encoding cartilage oligomeric matrix protein (COMP). This protein is predominantly found in the extracellular matrix of cartilage. Mutations in the COMP gene have been associated with syndromes of short stature. To verify that COMP is regulated by GH in vivo, we measured COMP levels in serum in short children treated with GH. The study included 113 short prepubertal children (14 girls and 99 boys) with a mean (+/- sd) age of 8.84 +/- 2.76 yr, height sd score of -2.74 +/- 0.67, and IGF-I sd score of -1.21 +/- 1.07 at the start of GH administration. Serum levels of COMP were 1.58 +/- 0.28, 1.83 +/- 0.28 (P < 0.0001), 1.91 +/- 0.28 (P < 0.0001), 1.78 +/- 0.28 (P < 0.001), and 1.70 +/- 0.24 (P < 0.05) microg/ml at baseline and after 1 wk and 1, 3, and 12 months, respectively.In conclusion, we have demonstrated that COMP expression is up-regulated by both GH and IGF-I in primary cultured human chondrocytes. Furthermore, serum levels of COMP increase after the start of GH treatment in short children.
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| 4. |
- Blair, J. C., et al.
(författare)
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Standard and low-dose IGF-I generation tests and spontaneous growth hormone secretion in children with idiopathic short stature
- 2004
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Ingår i: Clin Endocrinol (Oxf). ; 60:2, s. 163-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Abnormalities in the GH-IGF-I axis, consistent with GH insensitivity (GHI), have been reported in some patients with idiopathic short stature (ISS). The standard IGF-I generation test (IGFGT) has not demonstrated mild GHI in subjects with ISS. The aim of this study was to investigate the GH-IGF-I axis in ISS by performing standard and novel low-dose IGFGTs together with determination of spontaneous GH secretion. PATIENTS AND METHODS: Twenty-one (17 male) prepubertal children with ISS, mean age 8.3 years (4.5-12.2), mean height -3.48 SD (-5.40 to -1.79), mean peak GH to provocation with glucagon/clonidine 32.3 mU/l (14.1-66.0) were studied. Serum IGF-I and IGFBP-3 levels were measured during standard (GH 0.033 mg/kg/day x 4) and low (GH 0.011 mg/kg/day x 4) dose IGFGTs at 0, 12, 36 and 84 h. The low-dose IGFGT was performed in seven naive GH-deficient patients (4 male), mean age 8.5 years (range 4.1-11.1). Determination of spontaneous 24-h GH secretion was performed in the 21 ISS patients. RESULTS: Basal IGF-I and IGFBP-3 standard deviation scores (SDS) in ISS patients were -1.39 (-2.4-1.16) and -0.45 (-1.13-0.38), respectively, IGF-I being lower than IGFBP-3 (P < 0.0001). IGF-I increased in the standard IGFGT at 12 h (P < 0.005), 36 h (P < 0.001) and 84 h (P < 0.001); maximal increment 1.54 (-0.32-3.48), and in the low-dose test at 12 h (P < 0.005), 36 h (P < 0.001) and 84 h (P < 0.005); maximal increment 0.53 (0.08 to -1.23). IGFBP-3 SDS increased in the standard IGFGT at 36 h (P < 0.01) and 84 h (P < 0.001); maximal increment 0.72 (-0.44-1.96), and in the low-dose test at 84 h (P < 0.005); maximal increment 0.33 (-0.08-0.87). Five/19 patients with an IGF-I response > 2 x coefficient of variation (CV) of assay in the standard test failed to respond in the low-dose test, suggestive of mild GHI. In GH-deficient patients, IGF-I increased at each time point (P < 0.05) and IGFBP-3 at 36 h (P < 0.05). Mean GH secretion, expressed in SDS, compared with 66 normal stature controls was: basal GH -0.48 (-0.84-0.93), height of GH peaks compared with zero -0.36 (-1.26-1.51) (both P < 0.05), total GH secretion -0.76 (-1.22-0.42), total GH secretion above baseline -0.67 (-1.21-0.94) (both P < 0.01). CONCLUSIONS: In children with ISS, basal IGF-I and IGFBP-3 SDS values were below the mean, IGF-I showing a greater response in both IGFGTs. In the standard IGFGT, the IGF-I increase at 36 h was equal to that at 84 h. The low-dose IGFGT, in combination with the standard test, may identify patients with mild GHI.
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| 5. |
- Dahlgren, Jovanna, 1964, et al.
(författare)
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Prenatal cytokine exposure results in obesity and gender-specific programming.
- 2001
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Ingår i: American journal of physiology. Endocrinology and metabolism. - 0193-1849. ; 281:2, s. E326-34
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Tidskriftsartikel (refereegranskat)abstract
- Prenatal events appear to program hormonal homeostasis, contributing to the development of somatic disorders at an adult age. The aim of this study was to examine whether maternal exposure to cytokines or to dexamethasone (Dxm) would be followed by hormonal consequences in the offspring at adult age. Pregnant rats were injected on days 8, 10, and 12 of gestation with either human interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNF-alpha) or with Dxm. Control dams were injected with vehicle. All exposed offspring developed increased body weight (P < 0.05--0.001), apparently due to an increase of 30--40% in adipose tissue weight (P < 0.05--0.01). Corticosterone response to stress was increased in the IL-6 group (P < 0.05-0.01). Dxm-treated male rats exhibited blunted Dexamethasone suppression test results. In male rats, insulin sensitivity was decreased after IL-6 exposure (P < 0.01), whereas basal insulin was elevated in the TNF-alpha group (P < 0.01). In female rats, plasma testosterone levels were higher in all exposed groups compared with controls (P < 0.01--0.001), with the exception of Dxm-exposed offspring. Males in the TNF-alpha group showed decreased locomotor activity (P < 0.05), and females in the IL-6 group showed increased locomotor activity (P < 0.05). These results indicate that prenatal exposure to cytokines or Dxm leads to increased fat depots in both genders. In females, cytokine exposure was followed by a state of hyperandrogenicity. The results suggest that prenatal exposure to cytokines or Dxm can induce gender-specific programming of neuroendocrine regulation with consequences in adult life.
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| 6. |
- Erling, Ann, 1963, et al.
(författare)
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Psychological functioning in boys of short stature: Effects of different levels of growth hormone secretion
- 2002
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Ingår i: Acta Paediatrica. - 0803-5253. ; 91:9, s. 966-971
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To examine the relationship between growth hormone (GH) and psychological functioning, especially self-perception and well-being, in 60 prepubertal boys of short stature with a wide range of GH levels. Methods: A comparison was made of the well-being and self-perception of children with GH insufficiency, children with idiopathic short stature (ISS), a normative sample and healthy boys with normal stature. Results: Children with GH insufficiency had a more negative perception of their own physical appearance than the normative sample. They perceived themselves as more alert but also more inhibited than both the children with ISS and the healthy boys with normal stature. In comparison with the healthy boys with normal stature they perceived themselves as having more stability. The parents of the boys with GH insufficiency also perceived their children as being more stable compared with how the parents of boys with ISS perceived their children. To elucidate the effects of GH on psychological functioning a multiple regression analysis was performed. Conclusion: The lower the levels of GH the more inhibited were the boys of short stature, as perceived both by themselves and by their parents. The boys with GH insufficiency had a more negative perception of their physical appearance than the normative sample.
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| 7. |
- Fors, H, et al.
(författare)
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Currently used growth-promoting treatment of children results in normal bone mass and density. A prospective trial of discontinuing growth hormone treatment in adolescents.
- 2001
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Ingår i: Clinical endocrinology. - 0300-0664. ; 55:5, s. 617-24
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Tidskriftsartikel (refereegranskat)abstract
- The need for continued GH replacement in patients with childhood-onset GH deficiency (GHD) into adulthood has been recognized. The consequences of discontinuing GH treatment on bone mineralization in adolescent patients with GHD and short stature were examined over a period of 2 years.Forty adolescents (aged 16-21 years) treated with GH for more than 3 years and 16 closely matched healthy controls were studied. After a baseline visit, GH treatment was discontinued. The patients were then re-examined with the same protocol after 1 and 2 years. Twenty-one patients had continuing severe GHD into adulthood, while 19 patients were regarded as having sufficient endogenous GH secretion (GHS).At baseline, there were no differences between the groups in total bone mineral content (BMC) or bone mineral density (BMD). After 2 years without GH treatment, BMC increased similarly in the GHD and GHS groups. BMC of the lumbar spine (L2-L4) increased only in the GHD group. Lumbar spine BMD increased in the GHD and the GHS groups. No changes were observed in the femoral neck region. Biochemical measurements showed that carboxy-terminal cross-linked telopeptide of type I collagen (ICTP) and bone specific alkaline phosphates (ALP) were higher in the GHD and GHS groups at baseline compared with controls. Osteocalcin, carboxy-terminal propeptide of type I procollagen (PICP), ICTP and ALP decreased during the 2 years off treatment in both the GHD and GHS groups. PICP was also lower after 2 years in the GHD group compared with both the GHS group and controls.After discontinuation of GH therapy in adolescents at or near final height, there was a continued increase in BMC and BMD both for adolescents with growth hormone deficiency and for those classified as growth hormone sufficient. These groups did not differ from controls at baseline or after 2 years. In the growth hormone deficiency group, biochemical markers for bone formation decreased to levels below those in the growth hormone sufficient and healthy control groups. Although the number of patients and controls in this study were small, the results indicate that the present treatment of Swedish GH-deficient children to final height results in normal BMD.
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| 8. |
- Hellgren, Gunnel, 1961, et al.
(författare)
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Construction of a soluble human GH-receptor/EGF-receptor hybrid and its activation by GH
- 2004
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Ingår i: Cytokine. ; 25:6, s. 260-4
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Tidskriftsartikel (refereegranskat)abstract
- To develop a cell-free system that can be used to measure cytokine bioactivity we have designed a soluble hybrid molecule consisting of the extracellular domain of the GH-receptor (GHR) and the intracellular domain of the epidermal growth factor receptor (EGFR). A DNA construct encoding this hybrid-receptor was inserted into a baculoviral expression vector and expressed in Sf9-cells. Activation of the hybrid-receptor by ligand-induced dimerization can be measured as the incorporation of radiolabeled phosphate into a biotinylated tyrosine kinase peptide substrate. The kinase activity in samples stimulated with GH (10 ng/ml) increased 5-fold compared to samples without addition of GH. This is the first example of a functional hybrid-receptor where the transmembrane domain has been deleted. Our results suggest that such hybrid-receptors may be used for detection of GH and other cytokine-receptor activating substances in biological fluids.
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| 9. |
- Hesselmar, Bill, 1955, et al.
(författare)
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Born small for gestational age: relation to future allergy and asthma
- 2002
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Ingår i: Acta Paediatrica. - 0803-5253. ; 91:9, s. 992-4
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To evaluate whether intrauterine growth retardation (IUGR) protects against the development of allergy. METHODS: A case-control study of 1515 subjects (15-25 y), of whom 430 were cases (birthweight/length below -2 SD for gestational age). Birth data were from the national birth register. The frequencies of allergic diseases were evaluated by questionnaire. RESULTS: For the 950 who replied, the frequencies of allergic diseases were similar in cases and controls. CONCLUSION: IUGR does not protect against the development of allergy.
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| 10. |
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