The somatostatin analog octreotide inhibits GH-stimulated, but not IGF-I-stimulated, bone growth in hypophysectomized rats.
IGF-I mediates growth-promoting actions of GH. In the present study we investigated whether the somatostatin analog octreotide blunts the stimulatory effects of GH and/or IGF-I on bone growth in hypophysectomized rats infused for 6 d with vehicle, GH, or IGF-I. We found that octreotide significantly suppressed the GH-induced rise in liver IGF-I mRNA (-27%) and peptide (-32%) and the serum IGF-I level (-26%) and concomitantly inhibited GH-stimulated, but not IGF-I-stimulated, body weight gain (-31%), tibial epiphyseal width (-14%), and bone growth rate (-24%). Furthermore, octreotide significantly reduced the GH-induced increase in the number of IGF-I immunoreactive chondrocytes in all layers (except in the upper hypertrophic zone) of the tibial growth plate cartilage (P < 0.0001 for stem cell and proliferative zone; P < 0.0005 for lower hypertrophic zone). These findings demonstrate that octreotide does not interfere with IGF-I action, but does interfere with local GH-stimulated IGF-I production in the growth plate. Thus, besides inhibiting pituitary GH secretion, octreotide exerts inhibitory peripheral effects on GH-stimulated longitudinal bone growth.
Zapf
Jürgen
J
Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, 8091 Zurich, Switzerland. ndozaj@usz.unizh.ch
Gosteli-Peter
Martina
M
Weckbecker
Gisbert
G
Hunziker
Ernst B
EB
Reinecke
Manfred
M
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001846:Bone Development / Q000187:drug effects*; D004435:Eating / Q000187:drug effects; D013006:Growth Hormone / Q000037:antagonists & inhibitors*; D007016:Hypophysectomy; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D015282:Octreotide / Q000097:blood / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats
D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D015282:Octreotide