Corticotropin-releasing factor receptor subtype 1 and somatostatin modulating hypoxia-caused downregulated mRNA of pituitary growth hormone and upregulated mRNA of hepatic insulin-like growth factor-I of rats.
The study aims to examine the effects of restraint, cold, and in combination of hypoxia on pituitary GH mRNA and hepatic IGF-I mRNA and its protein in rats, and the potential involvement of corticotropin-releasing factor receptor subtype 1 (CRFR1) and SS in mediating the effects of continual hypoxia. Continual or intermittent hypoxia of 5 km (10.8% O2) was simulated in a hypobaric chamber. The mRNAs and peptides were determined using RT-PCR and Elisa or histochemistry. Continual hypoxia of 5 km markedly enhanced immunostaining pituitary GH and hepatic IGF-I for 1 and 2 days restoring afterward. The hypoxia for 5 days significantly reduced the pituitary GH mRNA and increased the hepatic IGF-I mRNA. Intermittent hypoxia of 5 km 4 h/day for 2 days, cold (4 degrees C) 4h/day for 2 days, and restraint 4 h/day for 2 days alone or in combination significantly enhanced immunostaining pituitary GH and hepatic IGF-I (except cold). The combined stresses had greater effects than single stresses alone. CRFR1 antagonist (CP154526) or SS antagonist (cysteamine) markedly blocked hypoxia-reduced pituitary GH mRNA and hypoxia-activated hepatic IGF-I mRNA, and further reduced hypoxia-reduced plasma IGF. In conclusion, hypoxia (continually or intermittently), restraint, cold alone or in combination modulate pituitary GH and hepatic IGF-I. The pituitary GH/GH mRNA and hepatic IGF-I/IGF-I mRNA, and plasma IGF-I are modified by hypoxia through SS and CRFR1 mediation.
Chen
Xue-Qun
XQ
Division of Neurobiology and Physiology, College of Life Sciences, Zhejiang University (Yuquan Campus), Hangzhou 310027, China.
Xu
Ning-Yi
NY
Du
Ji-Zeng
JZ
Wang
Yi
Y
Duan
Cunming
C
D000818:Animals; D003080:Cold Temperature; D003345:Corticosterone / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D013006:Growth Hormone / Q000235:genetics*; D000860:Hypoxia / Q000139:chemically induced / Q000235:genetics*; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism*; D012149:Restraint, Physical / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D000099052:CRF Receptor, Type 1
D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D013004:Somatostatin; D000099052:CRF Receptor, Type 1; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D003345:Corticosterone