title: Liver-derived IGF-I regulates GH secretion at the pituitary level in mice.
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.
authors.affiliation: Research Centre for Endocrinology and Metabolism, Sahlgrenska University Hospital, Göteborg SE-413 45, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Wallenius
authors.forename: K
authors.initials: K
authors.lastname: Sjögren
authors.forename: X D
authors.initials: XD
authors.lastname: Peng
authors.forename: S
authors.initials: S
authors.lastname: Park
authors.forename: V
authors.initials: V
authors.lastname: Wallenius
authors.forename: J L
authors.initials: JL
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Umaerus
authors.forename: H
authors.initials: H
authors.lastname: Wennbo
authors.forename: O
authors.initials: O
authors.lastname: Isaksson
authors.forename: L
authors.initials: L
authors.lastname: Frohman
authors.forename: R
authors.initials: R
authors.lastname: Kineman
authors.forename: C
authors.initials: C
authors.lastname: Ohlsson
authors.forename: J O
authors.initials: JO
authors.lastname: Jansson
mesh_terms: D000818:Animals; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009479:Neuropeptides / Q000502:physiology; D009929:Organ Size; D010902:Pituitary Gland / Q000378:metabolism*; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology; D011981:Receptors, Prolactin / Q000235:genetics
chemical_list: D009479:Neuropeptides; D011506:Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011981:Receptors, Prolactin; C035737:major urinary proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone