Tissue-specific regulation of growth hormone (GH) receptor and insulin-like growth factor-I gene expression in the pituitary and liver of GH-deficient (lit/lit) mice and transgenic mice that overexpress bovine GH (bGH) or a bGH antagonist.
GH has diverse biological actions that are mediated by binding to a specific, high-affinity cell surface receptor (GHR). Expression of GHR is tissue specific and a requirement for cellular responsiveness to GH. IGF-I is produced in multiple tissues and regulated in part by GH through GHR. In this study, we evaluated GHR and IGF-I mRNA expression in pituitary gland and compared the levels with those derived from liver of bovine GH transgenic, GH antagonist transgenic, lit/lit mice, and their respective controls using real-time RT-PCR. In liver, both GHR and IGF-I mRNA expressions were regulated in parallel with GH action in all three animal models, and there was a strong correlation between GHR and IGF-I mRNA levels. In the pituitary gland, increased expression of IGF-I mRNA in the pituitary of bovine GH transgenic mice was observed, whereas IGF-I expression in GH antagonist transgenic or lit/lit mice was similar to that observed in control animals. There were no differences of GHR mRNA levels in pituitary gland of any groups we examined. There was also no correlation between GHR and IGF-I mRNA levels in any group in the pituitary gland. In conclusion, we found that hepatic GHR and IGF-I mRNA levels were strongly correlated with each other in chronic GH excess or deficient state, and that regulation and correlation between local GHR and IGF-I mRNA levels induced by GH is different between liver and pituitary gland.
Iida
Keiji
K
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
Del Rincon
Juan P
JP
Kim
Dong-Sun
DS
Itoh
Emina
E
Nass
Ralf
R
Coschigano
Karen T
KT
Kopchick
John J
JJ
Thorner
Michael O
MO
D000818:Animals; D002417:Cattle; D004392:Dwarfism / Q000235:genetics; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics; D008822:Mice, Transgenic / Q000235:genetics; D010902:Pituitary Gland / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone