title: Metabolic effects of 20-kilodalton human growth hormone (20K-hGH) for adults with growth hormone deficiency: results of an exploratory uncontrolled multicenter clinical trial of 20K-hGH.
abstract: The biological effects of 20-kDa human GH (20K-hGH), which is produced in the pituitary by alternative splicing of GH mRNA and comprises approximately 6% of all GH in serum, have not been reported. We have investigated the metabolic effects of recombinant 20K-hGH in adult patients with GH deficiency in an exploratory study. Three doses of 20K-hGH (0.006, 0.012, and 0.024 mg/kg.d), were administered for 16 wk to three groups (consisting of 18 or 19 subjects), respectively. The 20K-hGH dose-dependently increased serum IGF-I and IGFBP-3 levels, and the lowest dose (0.006 mg/kg) was enough to normalize both hormones by wk 4. Serum osteocalcin levels and urinary deoxypyridinoline excretion were also dose-dependently increased. There was a significant decrease in body fat mass with an increase of lean body mass at the lowest dose of 0.006 mg/kg.d. Blood glucose and serum insulin were increased significantly at 4 wk only in the high-dose group (0.024 mg/kg). Glucose tolerance was slightly impaired in 26-39% of patients in all treatment groups as judged by oral glucose tolerance tests, but there was no development of overt diabetes. The major adverse event in the 20K-hGH treatment was peripheral edema, similar to the incidence reported for 22K-hGH. The data demonstrated that 20K-hGH had metabolic effects comparable to those of 22K-hGH in humans. The results suggest that 20K-hGH could be used to treat GH-deficient patients, although further studies may be required to investigate the optimum dose and superiority of 20K-hGH over 22K-hGH in a comparative study.
authors.affiliation: Research and Development Operations, Nihon Schering K.K., Osaka 532-0004, Japan. mahayakawa@schering.co.jp
authors.forename: Masakane
authors.initials: M
authors.lastname: Hayakawa
authors.forename: Yukio
authors.initials: Y
authors.lastname: Shimazaki
authors.forename: Toshio
authors.initials: T
authors.lastname: Tsushima
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Kato
authors.forename: Kazue
authors.initials: K
authors.lastname: Takano
authors.forename: Kazuo
authors.initials: K
authors.lastname: Chihara
authors.forename: Akira
authors.initials: A
authors.lastname: Shimatsu
authors.forename: Minoru
authors.initials: M
authors.lastname: Irie
mesh_terms: D000005:Abdomen; D000273:Adipose Tissue / Q000473:pathology; D000328:Adult; D001823:Body Composition; D001842:Bone and Bones / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000378:metabolism; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000172:deficiency*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D008661:Metabolism, Inborn Errors / Q000188:drug therapy; D008875:Middle Aged; D008970:Molecular Weight; D011788:Quality of Life; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D008055:Lipids; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D005947:Glucose