Abstract
Growth hormone (GH) modulates hematopoietic cell homeostasis and is associated with apoptosis control, but with limited mechanistic insights. Aim of the study was to determine whether GH therapeutic supplementation (GH-TS) could affect apoptosis of CD34+ cells enriched in hematopoietic progenitor cells of GH deficient (GHD) children. CD34+ cells from peripheral blood of 40 GHD children were collected before and in 3rd and 6th month of GH-TS and compared to 60 controls adjusted for bone age, sex, and pubertal development. Next, apoptosis assessment via different molecular techniques was performed. Finally, to comprehensively characterize apoptosis process, global gene expression profile was determined using genome-wide RNA microarray technology. Results showed that GH-TS significantly reduced spontaneous apoptosis in CD34+ cells (p < 0.01) and results obtained using different methods to detect early and late apoptosis in analyzed cells population were consistent. GH-TS was also associated with significant downregulation of several members of TNF-alpha superfamily and other genes associated with apoptosis and stress response. Moreover, the significant overexpression of cyto-protective and cell cycle-associated genes was detected. These findings suggest that recombinant human GH has a direct anti-apoptotic activity in hematopoietic CD34+ cells derived from GHD subjects in course of GH-TS.
Highlights
Growth hormone (GH) is essential for body growth during childhood and continues to stimulate anabolic processes in adults
We investigated the in vivo effects of GH therapeutic supplementation (GH-TS) on apoptosis in CD34+ cells enriched in hematopoietic progenitor cells (HPCs) collected from children with isolated GH deficient (GHD)
The comparison of levels of IGF-1 in GHD patients revealed that blood levels of IGF-1 were significantly higher in the 3rd and 6th month of GH-TS compared to GHD patients before therapy (229.5 and 214.3 vs. 125.0 ng/mL, respectively)
Summary
Growth hormone (GH) is essential for body growth during childhood and continues to stimulate anabolic processes in adults. GH exerts its anabolic effects largely indirectly via stimulation of insulin-like growth factor-1 (IGF1) production. Components of the GH–IGF1 axis make an important contribution to the development, function, and proliferation of different tissues [1]. The classical examples of IGF1-independent actions mediated through GHR are the proliferation of chondrocyte stem cells at bone growth plate [2], the fusion of myoblasts with nascent myotubes to increase muscle fiber size [3] or direct stimulation of neural stem cells to proliferate [4]. GHR has been shown to be expressed in different mature hematopoietic cells [5]
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