Growth Hormone Did Not Activate Its Intracellular Signaling Molecules in Rats’ Liver Hepatocytes During Early Life Period

BACKGROUND: Although growth hormone (GH) has essential roles in the growth of animals, it has no growth-promoting effect during infancy period. The molecular mechanism underlying lack of growth-promoting effect of GH during infancy period remains unclear. Important signaling pathways are mediated by GH, including Janus kinase 2 (JAK2), extracellular signal-regulated kinase 1/2 (ERK1/2), signal transducers, and activators of transcription 5, 3, and 1 (STATs 5, 3 and 1). OBJECTIVES: This study explored the underlying molecular mechanisms driving to the lack of growth-promoting effect of GH in the early stage of life by in vivo assessment of intracellular signal response (STAT5/ 3/ 1, JAK2 and ERK1/ 2) to GH at different physiological stages. METHODS: In this study, five age groups of rats (1-, 4-day-old, and 1-, 2-, 3-week-old) were selected. The rats were anesthetized using pentobarbital (100 mg/kg) and then received the rat GH (2mg/kg) via inferior vena cava injection. The control rats were injected with normal saline during the same period. The intracellular signal response to GH was assessed by Western blot analysis. RESULTS: JAK2 and STAT5 were expressed in 1-day and 4-day-old newborn rats and their expression levels were comparable with the levels of the 1-, 2-, and 3-week-old rats; however, JAK2/STAT5 phosphorylation was not observed in 1-day-old and 4-day-old newborn rats after stimulation with GH in the liver. Similar to JAK2 and STAT5, we did not detect STAT3/1 activation during infancy stages although basic STAT3 and STAT1 were also expressed in hepatocytes from newborn rats. In addition we detected ERK1/2 activation in 4-day-old, 1-, 2-, and 3-week-old rats but not in 1-day-old rats. CONCLUSIONS: JAK2, STAT5, STAT3, STAT1, and ERK1/2 were not simultaneously activated by GH in newborn rats; this finding may be one of the underlying mechanism of GH insensitivity in newborn rats.