20-kDa placental hGH-V has diminished diabetogenic and lactogenic activities compared with 22-kDa hGH-N while retaining antilipogenic activity

• Published in: American journal of physiology: endocrinology and metabolism Vol. 297; no. 3; pp. E629 - E637
• Main Authors: Vickers, M. H, Gilmour, S, Gertler, A, Breier, B. H, Tunny, K, Waters, M. J, Gluckman, P. D
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.09.2009
• Subjects: Animals; Body Weight - drug effects; Diabetes; Diabetes Mellitus, Experimental - chemically induced; Diet; Diet, Atherogenic; Drug Evaluation, Preclinical; Female; Gene expression; Growth Hormone - chemistry; Growth Hormone - pharmacology; Growth hormones; Human Growth Hormone - pharmacology; Hypolipidemic Agents - pharmacology; Lactation - drug effects; Lipogenesis - drug effects; Male; Molecular Weight; Peptide Fragments - pharmacology; Physiology; Placental Hormones - chemistry; Placental Hormones - pharmacology; Plasma; Protein Isoforms - chemistry; Protein Isoforms - pharmacology; Proteins; Rats; Rats, Wistar; Rodents
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00221.2009

1 Liggins Institute and National Research Centre for Growth and Development; 2 Neuren Pharmaceuticals, Auckland, New Zealand; 3 Hebrew University of Jerusalem, Rehovot, Israel; and 4 University of Queensland, Queensland, Australia Submitted 15 April 2009 ; accepted in final form 4 June 2009 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·g –1 ·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. placental growth hormone; insulin sensitivity; growth; adiposity Address for reprint requests and other correspondence: M. Vickers, Liggins Institute and the National Research Centre for Growth and Development, Univ. of Auckland, 2-6 Park Ave., Grafton, Auckland, New Zealand (e-mail: m.vickers{at}auckland.ac.nz )