Circulating non-22 kDa growth hormone isoforms in healthy children of normal stature: relation to height, body mass and pubertal development

Boguszewski, César Luiz; Jansson, C; Boguszewski, Margaret C. S.; Rosberg, Sten; Wikland, Kerstin Albertsson; Carlsson, Björn; Carlsson, Lena

doi:10.1530/eje.0.1370246

Cited by 18 publications

(13 citation statements)

References 46 publications

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“…The fraction of non-22 kDa GH isoforms in our newborns was similar to that in our group of non-pregnant women, despite marked differences in total GH concentrations between the groups. In addition, the neonatal values were also comparable to those reported by us in a group of healthy children at different stages of puberty (29). Hence, the normal proportion of circulating non-22 kDa GH isoforms in our study is in agreement with the previously reported half-life of GH in newborns (19).…”

Section: Total Gh (Mg/l)supporting

confidence: 92%

Growth hormone isoforms in newborns and postpartum women

Boguszewski

Boguszewski²,

Zegher³

et al. 2000

European Journal of Endocrinology

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The neonatal and postpartum periods are characterized by alterations in pituitary GH secretion. We have investigated the proportion of circulating non-22 kDa GH isoforms in newborns, in women within the early postpartum phase (just after the disappearance of placental GH from the maternal circulation) and in women during late postpartum (during the somatotroph recovery phase). We studied 10 newborns (7 males; 3 females; median postnatal age, 45 h), who had been admitted because of polycythaemia, 10 women in the early postpartum phase (median, 48 h after delivery; range, 42-54 h), 18 women in the late postpartum phase (median, 10 weeks after delivery; range, 3-25 weeks) and 9 healthy non-pregnant women. The proportion of non-22 kDa GH isoforms was determined by the 22 kDa GH exclusion assay, which is based on immunomagnetic extraction of 22 kDa GH from serum, and quantitation of non-22 kDa GH isoforms using a polyclonal GH assay. In newborns, non-22 kDa GH isoforms were measured in two arterial blood samples obtained with a 5-6 h interval. In the other groups, serum samples were obtained 40 min after an i.v. bolus administration of the GH secretagogue, GH releasing peptide-1 (GHRP-1).In newborns, the median proportion of non-22 kDa GH isoforms was 10% (range, 7.2-19.4%) and the values were similar in samples collected at different times. In early postpartum women, total GH levels after GHRP-1 were lower and the proportion of non-22 kDa GH isoforms was higher compared with the values in non-pregnant and late-postpartum women. In late postpartum, there was a partial recovery of GH response to GHRP-1, as shown by an increment in total GH levels, which was associated with a decrease in the fraction of non-22 kDa GH isoforms.In conclusion, we found that (i) the proportion of non-22 kDa GH isoforms in the newborn is comparable to that in the adult (non-pregnant women), (ii) in early postpartum, the non-22 kDa fraction is high within the small pool of readily releasable GH, (iii) in late postpartum, recovery of pituitary GH responsiveness is associated with a relative decrease in the release of non-22 kDa GH isoforms.

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Section: Total Gh (Mg/l)supporting

confidence: 92%

Growth hormone isoforms in newborns and postpartum women

Boguszewski

Boguszewski²,

Zegher³

et al. 2000

European Journal of Endocrinology

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“…Boguszewski et al (15) showed a significant positive correlation between the percentage of non-22K GH isoforms and BMI, weight sd score, or weight for height sd score in prepubertal children. This fact suggested that non-22K GH isoforms may be regulated by nutritional state.…”

Section: Discussionmentioning

confidence: 98%

“…Indirect estimation has been carried out by calculating the difference between total hGH and 22K (15)(16)(17). Other methods employed to estimate 20K include immunoaffinity chromatography (18), electrophoretic systems (19), and gelelectrophoretic-immunostaining-autoradiographic assay (20).…”

Section: Discussionmentioning

confidence: 99%

Serum Levels of 20-Kilodalton Human Growth Hormone (GH) Are Parallel Those of 22-Kilodalton Human GH in Normal and Short Children

Ishikawa¹,

Yokoya

Tachibana

et al. 1999

The Journal of Clinical Endocrinology &Amp; Metabolism

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Twenty-kilodalton human GH (20K), which is one of the human GH (hGH) variants, is thought to be produced by alternative premessenger ribonucleic acid splicing. However, its physiological role is still unclear due to the lack of a specific assay. We have measured serum 20K and 22-kDa hGH (22K) by specific ELISAs to investigate the physiological role of 20K in children.The subjects were 162 normal children, aged 1 month to 20 yr; 12 patients with GH deficiency (GHD), aged 11 months to 13 yr; 57 children with non-GHD short stature, aged 2-17 yr; and 13 girls with Turner's syndrome, aged 5 months to 15 yr. Samples were collected at random from normal children and were collected after hGH provocative tests and 3-h nocturnal sleep from GHD, non-GHD short stature, and Turner's syndrome children. The mean basal serum concentrations of 22K and 20K were 2.4 Ϯ 2.8 ng/mL and 152.3 Ϯ 184.0 pg/mL in normal boys and 2.5 Ϯ 3.1 ng/mL and 130.6 Ϯ 171.5 pg/mL in normal girls, respectively. The percentages of 20K (%20K) were 5.8 Ϯ 2.1% and 6.0 Ϯ 3.2% in 83 normal boys and 79 normal girls, respectively. There was no significant difference in %20K either among ages or between the prepubertal stage and the pubertal stage in normal boys and girls. The mean %20K values in basal samples of provocative tests in 12 patients with GHD, non-GHD short stature, and Turner's syndrome were 6.5 Ϯ 2.4%, 6.5 Ϯ 3.8%, and 5.9 Ϯ 3.2%, respectively. There was no significant difference in %20K among normal children and these growth disorders, and there was no significant difference in %20K throughout the hGH provocative tests and 3-h nocturnal sleep in these growth disorders. There was also no significant correlation between the percentage of 20K and the height SD score or body mass index in either normal children or subjects with these growth disorders.In conclusion, the %20K is constant, regardless of age, sex, puberty, height SD score, body mass index, and GH secretion status. The regulation of serum 20K levels remains to be established. (J Clin Endocrinol Metab 84: 98 -104, 1999)

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“…Of the circulating GH moieties in serum, the 22 kDa variant constitutes about two-thirds on the basis of size exclusion chromatography [25], and by far carries the major part of the GH bioactivity as it also has the greatest GH receptor affinity [26]. Some immunoassays, such as the Delfia and the immunofunctional GH assay, measure exclusively or almost exclusively the 22 kDa GH in serum [19, 27, 28]. The other GH variants (di- and polymers and the 20 kDa GH) also have longer plasma disappearance rates than 22 kDa GH, implying that there are several advantages to measuring specifically this variant at the peak level after GH stimulation tests when establishing relevant cut-off levels.…”

Section: Discussionmentioning

confidence: 99%

Variety in Growth Hormone Determinations due to Use of Different Immunoassays and to the Interference of Growth Hormone-Binding Protein

Ebdrup

Fisker²,

Sørensen³

et al. 1999

Horm Res Paediatr

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More than 30 years after their introduction, growth hormone (GH) immunoassays showed the poorest inter-laboratory agreement of the various hormone assays evaluated in 1998 by the UK National External Quality Assessment Scheme, in which different laboratories using different assays reported that analyses of identical samples differed two- to threefold in value. There is therefore an urgent requirement and desire within the scientific community, particularly within centres diagnosing and treating GH deficiency and acromegaly, to resolve this problem and to develop a GH assay(s) that measures solely all of the relevant components of circulating GH immunoreactivity. The main confounders in the estimation of GH levels (now that the use of GH standards other than that recommended by the World Health Organization has largely been eliminated) are GH heterogeneity, anti-GH antiserum binding site specificity and interference from circulating high-affinity GH-binding protein (GHBP). The effects of these factors are closely related. The present study investigates these factors, focussing on the influence of GHBP and antibody binding site specificity on various assays for GH. The findings lead the authors to suggest that a solution to the problem may be to develop a GH assay that measures specifically and solely all serum 22 kDa GH, as this is the major circulating fraction and carries the dominant GH bioactivity.

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Circulating non-22 kDa growth hormone isoforms in healthy children of normal stature: relation to height, body mass and pubertal development

Cited by 18 publications

References 46 publications

Growth hormone isoforms in newborns and postpartum women

Growth hormone isoforms in newborns and postpartum women

Serum Levels of 20-Kilodalton Human Growth Hormone (GH) Are Parallel Those of 22-Kilodalton Human GH in Normal and Short Children

Variety in Growth Hormone Determinations due to Use of Different Immunoassays and to the Interference of Growth Hormone-Binding Protein

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