Metabolic effects of 20 kDa and 22 kDa human growth hormones on adult male spontaneous dwarf rats

Ishikawa, Mayumi; Hiroi, Naoki; Kamioka, Takeshi; Tanaka, Toshiaki; Tachibana, Toshiaki; Ishikawa, Hiroshi; Miyachi, Yukitaka

doi:10.1530/eje.0.1450791

Cited by 20 publications

(11 citation statements)

References 31 publications

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“…Body weights and serum IGF-I increased dosedependently in both 20K-GH and 22K-GH treated groups [6]. Study on the osteo-anabolic effect of GH in cultured human osteoblastlike cells revealed that both 20K-GH and 22K-GH stimulated bone remodeling and exhibit equipotent anabolic effects on skeletal tissues [7].…”

Section: Biological Effectmentioning

confidence: 99%

20K-GH and its use in detecting GH abuse

Irie

Ueki

Kishikawa

et al. 2009

Growth Hormone & IGF Research

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Section: Biological Effectmentioning

confidence: 99%

20K-GH and its use in detecting GH abuse

Irie

Ueki

Kishikawa

et al. 2009

Growth Hormone & IGF Research

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“…This isoform is generated by alternative splicing within exon 3 of the GH primary transcript, resulting in the deletion of residues 32-46 of 22-kDa GH (1,6). The 20-kDa GH has growthpromoting and lipolytic activities similar to those of 22-kDa GH (18,25) but has reduced antinatriuretic activity (21). Although these observations suggest that it has a slightly different metabolic profile, the physiological role of 20-kDa GH is not known.…”

mentioning

confidence: 99%

Physiological and pharmacological regulation of 20-kDa growth hormone

Leung

Howe

Gui

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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The 20-kDa growth hormone (GH) is generated from alternative splicing of the primary transcript of full-length 22-kDa GH. We have studied the regulation of 20-kDa GH over a range of pathophysiological conditions and in response to pharmacological stimulation using isoformspecific enzyme-linked immunosorbent assays (ELISAs). Mean 24-h levels of 20-and 22-kDa GH were higher in acromegaly and lower in GH deficiency than in normal subjects, with the 20-to-22-kDa ratio not different between the three groups. In normal subjects, 20-kDa GH was secreted in a pulsatile manner throughout the day, with peaks coinciding with those of 22-kDa GH. However, the half-life of 20-kDa GH (18.7 Ϯ 0.8 min) was significantly longer than that of 22-kDa GH (14.7 Ϯ 0.8 min; P Ͻ 0.02). Insulin-induced hypoglycemia, androgen, and oral estrogen caused a parallel and proportionate increase in both isoforms. Octreotide suppressed 20-kDa less rapidly than 22-kDa GH in blood. Administration of recombinant 22-kDa GH in normal subjects rapidly reduced the 20-kDa GH levels. In conclusion, 20-kDa GH is cosecreted with and circulates at a constant proportion of 22-kDa GH. The 20-kDa GH level is reduced by administration of exogenous 22-kDa GH, suggesting rapid negative feedback regulation on pituitary release.androgen; estrogen; deconvolution analysis; insulin-induced hypoglycemia GROWTH HORMONE (GH) exists as a mixture of multiple molecular forms arising from both posttranscriptional and posttranslational modifications (1, 23). The major isoform of molecular size 22 kDa comprises 191 amino acid residues, whereas the second-most abundant isoform is 20 kDa in size and accounts for ϳ10% of total GH in the pituitary (19). This isoform is generated by alternative splicing within exon 3 of the GH primary transcript, resulting in the deletion of residues 32-46 of 22-kDa GH (1, 6). The 20-kDa GH has growthpromoting and lipolytic activities similar to those of 22-kDa GH (18, 25) but has reduced antinatriuretic activity (21). Although these observations suggest that it has a slightly different metabolic profile, the physiological role of 20-kDa GH is not known.Recently, studies using a highly specific enzymelinked immunosorbent assay (ELISA) for 20-kDa GH have revealed that it circulates at a constant proportion to 22-kDa GH under a variety of physiological and pathophysiological conditions (12). However, it remains to be determined whether 20-kDa GH is regulated differently from 22-kDa GH. To gain more insight in the regulation of 20-kDa GH in blood, we have compared the serum levels of 20-and 22-kDa GH 1) in health and disease, 2) in response to acute stimulation and suppression, 3) in response to gonadal steroids, and 4) in response to exogenous recombinant 22-kDa GH. SUBJECTS AND METHODSSubjects and study design. Five separate studies were performed to investigate the physiological and pharmacological regulation of 20-kDa GH secretion (14-17, 20, 33). The clinical data of some of these studies have been previously published in part. All study protocols w...

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“…Subsequent studies have yielded conflicting information in this regard, perhaps in part due to species differences [29][30][31]. The growth promoting activity of 20K-GH in vivo has been found to be similar to that of 22K-GH in the rat [10,[32][33][34] despite diminished affinity of 20K-GH for the GHR (see below). In the obese mouse 20K-GH had mildly diminished growth-promoting and lipolytic activity compared to 22K-GH [35], but the two GH isoforms had equipotent lipolytic activity in chicken adipose tissue [36].…”

Section: K-ghmentioning

confidence: 99%