Liver-derived IGF-I regulates GH secretion at the pituitary level in mice

Endocrinology. 2001 Nov;142(11):4762-70. doi: 10.1210/endo.142.11.8478.

Abstract

We have reported that liver-specific deletion of IGF-I in mice (LI-IGF-I-/-) results in decreased circulating IGF-I and increased GH levels. In the present study, we determined how elimination of hepatic IGF-I modifies the hypothalamic-pituitary GH axis to enhance GH secretion. The pituitary mRNA levels of GH releasing factor (GHRF) receptor and GH secretagogue (GHS) receptor were increased in LI-IGF-I-/- mice, and in line with this, their GH response to ip injections of GHRF and GHS was increased. Expression of mRNA for pituitary somatostatin receptors, hypothalamic GHRF, somatostatin, and neuropeptide Y was not altered in LI-IGF-I-/- mice, whereas hypothalamic IGF-I expression was increased. Changes in hepatic expression of major urinary protein and the PRL receptor in male LI-IGF-I-/- mice indicated an altered GH release pattern most consistent with enhanced GH trough levels. Liver weight was enhanced in LI-IGF-I-/- mice of both genders. In conclusion, loss of liver-derived IGF-I enhances GH release by increasing expression of pituitary GHRF and GHS receptors. The enhanced GH release in turn affects several liver parameters, in line with the existence of a pituitary-liver axis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Female
  • Growth Hormone / blood
  • Growth Hormone / genetics
  • Growth Hormone / metabolism*
  • Growth Hormone-Releasing Hormone / pharmacology
  • Hypothalamus / metabolism
  • Insulin-Like Growth Factor I / analysis
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / physiology*
  • Liver / anatomy & histology
  • Liver / metabolism*
  • Male
  • Mice
  • Mice, Knockout / genetics
  • Neuropeptides / physiology
  • Organ Size
  • Pituitary Gland / metabolism*
  • Proteins / genetics
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / physiology
  • Receptors, Prolactin / genetics

Substances

  • Neuropeptides
  • Proteins
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Prolactin
  • major urinary proteins
  • Insulin-Like Growth Factor I
  • Growth Hormone
  • Growth Hormone-Releasing Hormone