title: 20-kDa placental hGH-V has diminished diabetogenic and lactogenic activities compared with 22-kDa hGH-N while retaining antilipogenic activity.
abstract: Placental human growth hormone-variant (hGH-V) and pituitary human growth hormone-N (hGH-N) are of identical size (22 kDa) but differ in 13 residues scattered throughout the protein. Several isoforms of GH are produced by the hGH-N and hGH-V genes including a 20-kDa hGH-V resulting from a 45-bp deletion caused by the use of an alternative acceptor site within exon 3. To date, the biological properties of the 20-kDa GH-V have not been characterized in vivo. Using young male Wistar rats fed either chow or a high-fat (HF) diet for 4 wk postweaning, we investigated the effect of 7 days treatment with either 22-kDa hGH-N, 20-kDa hGH-V (5 ug x g(-1) x day(-1) sc), or vehicle on body composition and endocrine and metabolic profiles. Total body growth (absolute weight gain and linear growth trajectory) in the 20-kDa hGH-V-treated animals was intermediary between that of control and hGH-N-treated animals. Both 22-kDa hGH-N and 20-kDa hGH-V significantly reduced total body fat mass compared with control animals, and there were no differences between the GH isoforms in anti-lipogenic activity in animals fed the HF diet. Fasting plasma insulin and C peptide were significantly increased in animals on the HF diet and further increased by hGH-N but were unchanged in 20-kDa hGH-V-treated animals compared with saline-treated controls. Plasma volume as assessed by hematocrit was increased in hGH-N-treated animals but was unchanged in 20-kDa hGH-V-treated animals compared with controls. Furthermore, 20-kDa hGH-V had reduced lactogenic (prolactin receptor mediated) activity characteristic of hGH-N as tested in vitro compared with the 20-kDa hGH-N and 22-kDa hGH-N variants. In summary, placental 20-kDa hGH-V retains some of the growth-promoting and all antilipogenic activities of pituitary 22-kDa hGH-N but has diminished diabetogenic and lactogenic properties compared with the native 22-kDa hGH-N.
authors.affiliation: Liggins Institute and the National Research Centre for Growth and Development, Auckland, New Zealand. m.vickers@auckland.ac.nz
authors.forename: M H
authors.initials: MH
authors.lastname: Vickers
authors.forename: S
authors.initials: S
authors.lastname: Gilmour
authors.forename: A
authors.initials: A
authors.lastname: Gertler
authors.forename: B H
authors.initials: BH
authors.lastname: Breier
authors.forename: K
authors.initials: K
authors.lastname: Tunny
authors.forename: M J
authors.initials: MJ
authors.lastname: Waters
authors.forename: P D
authors.initials: PD
authors.lastname: Gluckman
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced*; D004036:Diet, Atherogenic; D004353:Drug Evaluation, Preclinical; D005260:Female; D013006:Growth Hormone / Q000737:chemistry / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007774:Lactation / Q000187:drug effects*; D050155:Lipogenesis / Q000187:drug effects*; D008297:Male; D008970:Molecular Weight; D010446:Peptide Fragments / Q000494:pharmacology*; D010926:Placental Hormones / Q000737:chemistry / Q000494:pharmacology*; D020033:Protein Isoforms / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: C064980:GH2 protein, human; D000960:Hypolipidemic Agents; D010446:Peptide Fragments; D010926:Placental Hormones; D020033:Protein Isoforms; C404802:human growth hormone 22K; D019382:Human Growth Hormone; D013006:Growth Hormone