Impaired growth hormone receptor signaling during non-catch-up growth in rats born small for gestational age.
OBJECTIVE
Non-catch-up growth (NCG) in children born small for gestational age (SGA) is associated with growth hormone (GH) resistance, although the mechanisms of this association are unknown. Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling is involved in GH signal transduction. This study examined the role of JAK/STAT signaling in GH resistance of SGA rats.


METHODS
NCG-SGA was induced by uterine artery ligation in pregnant rats. NCG-SGA rats were treated with GH for 7 days and rats appropriate for gestational age (AGA) served as controls. Phosphorylation of JAK2/STAT5 and expression of GH receptor, suppressor of cytokine signaling 2 (SOCS-2) and cytokine-inducible SH2-containing protein (CIS) in the liver were determined by Western blotting. The expression of insulin-like growth factor 1 (IGF-1) mRNA was examined by the reverse transcription-polymerase chain reaction.


RESULTS
GH treatment significantly increased body weight and length growth rate in AGA but not in NCG-SGA rats. The increase in serum IGF-1 level and expression of IGF-1 mRNA in response to GH treatment in NCG-SGA rats was significantly less than in AGA rats. GH-induced increase in phosphorylation of JAK2/STAT5 in response to acute GH stimulation was significantly lower in NCG-SGA rats compared to AGA controls. SOCS-2 and CIS expressions significantly increased in NCG-SGA rats following GH treatment.


CONCLUSIONS
GH resistance in NCG-SGA rats is associated with impaired JAK/STAT signaling and upregulated SOCS-2 and CIS expression.
Huang
Yuefang
Y
Department of Pediatrics, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Du
Minlian
M
Zhuang
Siqi
S
Shen
Zhenyu
Z
Li
Yijuan
Y
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D004195:Disease Models, Animal; D005260:Female; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007230:Infant, Low Birth Weight / Q000502:physiology*; D007231:Infant, Newborn; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000502:physiology; D008099:Liver / Q000502:physiology; D008297:Male; D011247:Pregnancy; D012313:RNA / Q000737:chemistry / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*
D050799:STAT5 Transcription Factor; D050826:Suppressor of Cytokine Signaling Proteins; D019382:Human Growth Hormone; D012313:RNA; D007334:Insulin-Like Growth Factor I