Abstract
The growth hormone (GH) plays a key role in the regulation of metabolic processes in an organism. Determination of the correct structure and functioning of the growth hormone receptor (GHR) allowed for a more detailed research of its post-receptor regulators, which substantially influences its signal transduction. This review is focused on the description of the post-receptor inhibitors of the GHR-JAK2-STAT pathway, which is one of the most important pathways in the transduction of the somatotropic axis signal. The aim of this review is the short characterization of the main post-receptor inhibitors, such as: cytokine-inducible SH2-containing protein (CIS), Suppressors of Cytokine Signaling (SOCS) 1, 2 and 3, sirtuin 1 (SIRT1), protein inhibitors of activated STAT (PIAS) 1, 3 and PIAS4, protein tyrosine phosphatases (PTP) 1B and H1, Src homology 2 (SH2) domain containing protein tyrosine phosphatase (SHP) 1, 2 and signal regulatory protein (SIRP) α1. The equilibrium between these regulators activity and inhibition is of special concern because, as many studies showed, even slight imbalance may disrupt the GH activity causing serious diseases. The regulation of the described inhibitors expression and activity may be a point of interest for pharmaceutical industry.
Highlights
The review is focused on the post-receptor regulators of growth hormone receptor (GHR) transduction pathway, which affect the axis in an inhibitory manner, such as cytokine-inducible Src homology 2 (SH2)-containing protein (CIS), suppressor of cytokine signaling (SOCS) 1, SOCS2, SOCS3, sirtuin 1 (SIRT1), signal regulatory protein α1 (SIRPα1), protein inhibitor of activated signal transducer and activator of transcription (STAT) (PIAS), protein tyrosine phosphatase-1B (PTP-1B), protein tyrosine phosphatases (PTP)-H1, SH2 domain containing protein tyrosine phosphatase-1 (SHP-1) and SHP-2
The several physiological inhibitors of the GHR-Janus kinase 2 (JAK2)-STAT pathway, which act through numerous different mechanisms, have been presented
It was stated that STAT3 and, in particular, STAT5 activated by GHR may participate in the ontogenesis and cancer progression
Summary
Growth hormone (GH), one of the major hormones of the somatotropic axis, is a 191-amino acid protein found in many isoforms [1]. IGF-1 is a very potent growth factor which stimulates to growth all cell types [18] playing a key role in pre- and postnatal growth It directly affects glucose and protein metabolism [19]. During postnatal period of life, endogenous and exogenous IGF-1 was shown to promote the regeneration of different tissues, including the bone [20], muscle [21], nerve [22,23] and pancreas [24,25] These pro-regenerative effects of IGF-1 are associated with reduction in the release of pro-inflammatory cytokines and stimulation of the release of anti-inflammatory cytokines [24]. GH and IGF-1 may participate in the therapeutic effect of other molecules such as ghrelin in pancreas [26], colon [27,28] or oral mucosa [29]
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