Liver-derived IGF-I regulates GH secretion at the pituitary level in mice.
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.
Wallenius
K
K
Research Centre for Endocrinology and Metabolism, Sahlgrenska University Hospital, Göteborg SE-413 45, Sweden.
Sjögren
K
K
Peng
X D
XD
Park
S
S
Wallenius
V
V
Liu
J L
JL
Umaerus
M
M
Wennbo
H
H
Isaksson
O
O
Frohman
L
L
Kineman
R
R
Ohlsson
C
C
Jansson
J O
JO
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
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