New insights into growth hormone�s actions on the macrophage: Implications for non-growth related actions of growth hormone

Abstract

hormonal and metabolic factors, including blood glucose levels, exercise, sex hormones, glucocorticoids and thyroid hormone. At the cellular level, the pleiotropic action of GH is elicited by its interaction with the GH receptor (GHR). GHR belongs to class I cytokine receptor superfamily that includes receptors for PRL, leptin and interleukins. The predicted molecular mass of GHR is ~70 kDa. An initiating event in this interaction is the activation of janus kinase 2 (JAK2), a GHR-associated tyrosine kinase. According to the original model, a single molecule of GH sequentially binds to two GHRs to induce dimer formation, which then increases the affinity of each GHR for JAK2. However, this original concept was revised recently by a study, which indicates GHRs either exist as a dimer 2 or as a heterodimer with the prolactin receptor 3 and that GH binding brings about a conformational change in the dimer that is important for the postreceptor signalling cascade, including activation of JAK2. Activated JAK2 phosphorylates itself and also the tyrosine residues in the cytoplasmic domain of GHR. These phosphotyrosines are thought to form high-affinity binding sites that recruit a variety of signalling proteins containing phosphotyrosine-binding domains, including signal transducers and activators of transcription (STAT) family proteins. The activated GHR-JAK2 complex can phosphorylate at least four members of the STAT family (STATs 1, 3, 5A and 5B), leading to their dimerisation, nuclear translocation and activation of transcription. Another pathway important in GH-regulated gene transcription is the mitogen-activated

Nitric oxide blocks the development of the human parasiteSchistosoma japonicum

“…Interestingly, removal of the pituitary gland and thyroid/parathyroid glands from rats before infection with S. mansoni resulted in increasing worm burdens, worm development, oviposition, and miracidial development (15). Indeed, growth hormone and thyroid hormones have been demonstrated to directly induce iNOS expression and increase iNOS activity by influencing the maturation and function of immune cells, such as macrophages (29)(30)(31)(32)(33). These results strongly support the important role of NO in the development of Schistosoma.…”

Growth hormone-mediated reprogramming of macrophage transcriptome and effector functions

“…Furthermore, a defective expression of genes in the myeloid cell differentiation pathway was demonstrated in peripheral leukocytes of df/df mice compared to N mice 33 , further suggesting this inability of monocytes to migrate to tissues in the absence of GH. Conversely, Kumar and Menon 34 reported that in vivo GH treatment also enhances monocyte migration to tissue, which can improve the ability to fight infection in local tissues. This evidence, combined with our current findings, indicated that GH may exert a significant impact on the maturation, activation, and functionality of effector macrophages.…”

Terapi Human Growth Hormone (HGH) untuk Anak dengan Non-Growth Hormone Deficiency (Non-GHD)

“…2 Problematika penggunaan GH pada non-GHD adalah kontroversi terkait dosis dan saat memulai pemberian, kemungkinan efek samping jangka panjang yang diperkirakan dapat menyebabkan keganasan. 3,4 Mekanisme Kerja GH Pada tingkat sel, mekanisme kerja GH tergantung pada interaksi dengan reseptor GH, diikuti dengan aktivasi janus kinase-2 transduser dan aktivasi kaskade transkripsi sinyal. Efek GH terjadi pada jaringan seperti hepar, tulang, otot, sel adiposit.…”

“…Efek GH terjadi pada jaringan seperti hepar, tulang, otot, sel adiposit. 3 Ekstraksi substansi GH dari lobus anterior berhasil pada tahun 1921 dan aplikasinya pada manusia dimulai tahun 1958. Sebagai pusat regulator endokrin post natal, GH mengkode 217 asam amino yang akan menyebabkan terjadinya pembelahan proteolitik dari sinyal peptida, menghasilkan rantai tunggal polipetoda 191 asam amino dengan berat molekul 22 kDa.…”

“…Sebagai pusat regulator endokrin post natal, GH mengkode 217 asam amino yang akan menyebabkan terjadinya pembelahan proteolitik dari sinyal peptida, menghasilkan rantai tunggal polipetoda 191 asam amino dengan berat molekul 22 kDa. 3,5 GH disintesis dan disekresi oleh somatotropin pada kelenjar hipofisis anterior di bawah kontrol neuronal dan jalur protein kinase (Ras-MAP). GH dan insulin berada pada jalur sinyal yang sama.…”