title: Comparison of pulsatile vs. continuous administration of human placental growth hormone in female C57BL/6J mice.
abstract: Exogenous growth hormone has different actions depending on the method of administration. However, the effects of different modes of administration of the placental variant of growth hormone on growth, body composition and glucose metabolism have not been investigated. In this study, we examined the effect of pulsatile vs. continuous administration of recombinant variant of growth hormone in a normal mouse model. Female C57BL/6J mice were randomized to receive vehicle or variant of growth hormone (2 or 5 mg/kg per day) by daily subcutaneous injection (pulsatile) or osmotic pump for 6 days. Pulsatile treatment with 2 and 5 mg/kg per day significantly increased body weight. There was also an increase in liver, kidney and spleen weight via pulsatile treatment, whereas continuous treatment did not affect body weight or organ size. Pulsatile treatment with 5 mg/kg per day significantly increased fasting plasma insulin concentration, whereas with continuous treatment, fasting insulin concentration was not significantly different from the vehicle-treated control. However, a dose-dependent increase in fasting insulin concentration and decrease in insulin sensitivity, as assessed by HOMA, was observed with both modes of treatment. At 5 mg/kg per day, hepatic growth hormone receptor expression was increased compared to vehicle-treated animals, by both modes of administration. Pulsatile variant of growth hormone did not alter the plasma insulin-like growth factor-1 concentration, whereas a slight decrease was observed with continuous variant of growth hormone treatment. Neither pulsatile nor continuous treatment affected hepatic insulin-like growth factor-1 mRNA expression. Our findings suggest that pulsatile variant of growth hormone treatment was more effective in stimulating growth but caused marked hyperinsulinemia in mice.
authors: Liggins Institute, University of Auckland, Auckland, New Zealand.|Gravida: National Centre for Growth and Development, Auckland, New Zealand.|The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors: Shutan
authors: S
authors: Liao
authors: Liggins Institute, University of Auckland, Auckland, New Zealand.|Gravida: National Centre for Growth and Development, Auckland, New Zealand.
authors: Mark H
authors: MH
authors: Vickers
authors: Liggins Institute, University of Auckland, Auckland, New Zealand.
authors: Angharad
authors: A
authors: Evans
authors: Liggins Institute, University of Auckland, Auckland, New Zealand.|Gravida: National Centre for Growth and Development, Auckland, New Zealand.
authors: Joanna L
authors: JL
authors: Stanley
authors: Liggins Institute, University of Auckland, Auckland, New Zealand.|Gravida: National Centre for Growth and Development, Auckland, New Zealand.
authors: Philip N
authors: PN
authors: Baker
authors: Liggins Institute, University of Auckland, Auckland, New Zealand. j.perry@auckland.ac.nz.|Gravida: National Centre for Growth and Development, Auckland, New Zealand. j.perry@auckland.ac.nz.
authors: Jo K
authors: http://orcid.org/0000-0002-4418-947X
authors: JK
authors: Perry
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects*; D002460:Cell Line; D004334:Drug Administration Schedule; D004435:Eating / Q000187:drug effects*; D005260:Female; D019382:Human Growth Hormone / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D051379:Mice; D013154:Spleen / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007328:Insulin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I
keywords: Delivery methods; Insulin sensitivity; Mice; Placental growth hormone