Abstract
ABSTRACT Porcine growth hormone (pGH) is most important hormone which is involved in the growth and development of pig. However, a series of studies have indicated that neonatal pig is insensitive to pGH; the reason for this phenomenon is still not fully understood. In this work, we try to investigate this issue from the angle of intracellular signaling induced by pGH. In the present study, porcine hepatocytes from neonatal pig were used as a model, and confocal laser scanning microscopy (CLSM), Western blot, co-immunoprecipitation and colocalization assay were used to study pGH’s signaling properties in hepatocytes of neonatal pig and explore the possible mechanism(s) for why intracellular signaling is insensitive to pGH. The results indicated that Janus kinase 2 and signal transducers and activators of transcription 5/3/1 (JAK2-STATs) signaling are not activated. We further investigated the possible mechanism(s) by which JAK2-STATs’ signaling is not activated by pGH and growth hormone receptor (GHR) and found that the negative regulatory molecules of JAK2-STATs signaling may be associated with this phenomenon in the hepatocytes of neonatal pig. In addition, we also explored pGH’s biology in hepatocytes from neonatal pig, it can be found that pGH/GHR could translocate into the cell nucleus, which implies that pGH/GHR may exhibit physiological roles based on their nuclear localization. We found that pGH could not trigger intracellular signaling in the hepatocytes of neonatal pigs, but not young pigs, which provides an important explanation for why the growth of neonatal pig is GH independent.
Highlights
Growth hormone (GH) plays important roles in the regulation of growth and development in mammals (Lan et al 2017)
The results indicated that growth hormone receptor (GHR) were expressed on the cell cytoplasm and membrane, and there were no difference in the pGHR expression levels in 1–7 days old pig
The researchers have analyzed the reason for why GH is not sensitive in neonates; they proposed that GHR’s expression is low in neonatal animals, which leads to low GH binding, which, in turn, results in low circulating IGF-1 (Martinez et al 2013)
Summary
Growth hormone (GH) plays important roles in the regulation of growth and development in mammals (Lan et al 2017). GH exerts its physiological functions by binding to growth hormone receptor (GHR) (Brooks and Waters 2010). Janus Kinase 2 (JAK2) is activated by tyrosine phosphorylation, which subsequently phosphrylated signal transducer and activator of transcription (STAT) and extracellular regulated protein kinases (ERK1/2) ERK1/2 (Brooks et al 2014; Waters 2016). These active signaling proteins transport into the cell nuclei, where they regulate gene expression. PGH could stimulate the liver of neonatal pig to express IGF-1 mRNA and improve the level of circulating IGF-1, the ability of the production of IGF-1 is weaker than that of young pig (Rehfeldt et al 2004). The concentration of pGH in the circulation of neonatal pig is very low (Lan et al 2015), and pGHR
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