In this review, we analyze the effects of growth hormone on a number of tissues and organs and its putative role in the longitudinal growth of an organism. We conclude that the hormone plays a very important role in maintaining the homogeneity of tissues and organs during the normal development of the human body or after an injury. Its effects on growth do not seem to take place during the fetal period or during the early infancy and are mediated by insulin-like growth factor I (IGF-I) during childhood and puberty. In turn, IGF-I transcription is dependent on an adequate GH secretion, and in many tissues, it occurs independent of GH. We propose that GH may be a prohormone, rather than a hormone, since in many tissues and organs, it is proteolytically cleaved in a tissue-specific manner giving origin to shorter GH forms whose activity is still unknown.

BackgroundAccumulating evidence suggests that growth hormone (GH) may play a major role in the regulation of postnatal neurogenesis, thus supporting the possibility that it may be also involved in promoting brain repair after brain injury. In order to gain further insight on this possibility, in this study we have investigated the pathways signaling the effect of GH treatment on the proliferation and survival of hippocampal subgranular zone (SGZ)-derived neurospheres.ResultsOur results demonstrate that GH treatment promotes both proliferation and survival of SGZ neurospheres. By using specific chemical inhibitors we have been also able to demonstrate that GH treatment promotes the activation of both Akt-mTOR and JNK signaling pathways, while blockade of these pathways either reduces or abolishes the GH effects. In contrast, no effect of GH on the activation of the Ras-ERK pathway was observed after GH treatment, despite blockade of this signaling path also resulted in a significant reduction of GH effects. Interestingly, SGZ cells were also capable of producing GH, and blockade of endogenous GH also resulted in a decrease in the proliferation and survival of SGZ neurospheres.ConclusionsAltogether, our findings suggest that GH treatment may promote the proliferation and survival of neural progenitors. This effect may be elicited by cooperating with locally-produced GH in order to increase the response of neural progenitors to adequate stimuli. On this view, the possibility of using GH treatment to promote neurogenesis and cell survival in some acquired neural injuries may be envisaged.

Aims Obesity, diabetes and cardiovascular disease are associated with COVID‐19 risk and severity. Because epicardial adipose tissue (EAT) expresses ACE2, we wanted to identify the main factors associated with ACE2 levels and its cleavage enzyme, ADAM17, in epicardial fat. Materials and methods Epicardial and subcutaneous fat biopsies were obtained from 43 patients who underwent open‐heart surgery. From 36 patients, biopsies were used for RNA expression analysis by real‐time PCR of ACE1, ACE2 and ADAM17 . From 8 patients, stromal vascular cells were submitted to adipogenesis or used for studying the treatment effects on gene expression levels. Soluble ACE2 was determined in supernatants by ELISA. Results Epicardial fat biopsies expressed higher levels of ACE2 (1.53 [1.49‐1.61] vs 1.51 [1.47‐1.56] a.u., P < .05) and lower ADAM17 than subcutaneous fat (1.67 [1.65‐1.70] vs 1.70 [1.66‐1.74] a.u., P < .001). Both genes were increased in epicardial fat from patients with type 2 diabetes mellitus (T2DM) (1.62 [1.50‐2.28] vs 1.52 [1.49‐1.55] a.u., P = .05 for ACE2 and 1.68 [1.66‐1.78] vs 1.66 [1.63‐1.69] a.u., P < .05 for ADAM17 ). Logistic regression analysis determined that T2DM was the main associated factor with epicardial ACE2 levels ( P < .01). The highest ACE2 levels were found on patients with diabetes and obesity. ACE1 and ACE2 levels were not upregulated by antidiabetic treatment (metformin, insulin or thiazolidinedione). Its cellular levels, which were higher in epicardial than in subcutaneous stromal cells (1.61 [1.55‐1.63] vs 1 [1‐1.34]), were not correlated with the soluble ACE2. Conclusion Epicardial fat cells expressed higher levels of ACE2 in comparison with subcutaneous fat cells, which is enhanced by diabetes and obesity presence in patients with cardiovascular disease. Both might be risk factors for SARS‐CoV‐2 infection.

This study was designed to investigate a possible role of the N-terminal tripeptide of insulin-like growth factor-1 (IGF-I), Gly-Pro-Glu (GPE), physiologically generated in neurons following IGF-I-specific cleavage, in promoting neural regeneration after an injury. Primary cultures of mouse neural stem cells (NSCs), obtained from 13.5 Days post-conception (dpc) mouse embryos, were challenged with either GPE, growth hormone (GH), or GPE + GH and the effects on cell proliferation, migration, and survival were evaluated both under basal conditions and in response to a wound healing assay. The cellular pathways activated by GPE were also investigated by using specific chemical inhibitors. The results of the study indicate that GPE treatment promotes the proliferation and the migration of neural stem cells in vitro through a mechanism that involves the activation of extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase PI3K-Akt pathways. Intriguingly, both GPE effects and the signaling pathways activated were similar to those observed after GH treatment. Based upon the results obtained from this study, GPE, as well as GH, may be useful in promoting neural protection and/or regeneration after an injury.

BackgroundNeural stem cells (NSC) have been extensively used as a tool to investigate the mechanisms responsible for neural repair, and they have been also considered as the source for a series of promising replacement therapies in various neurodegenerative diseases. However, their use is limited by their relative rarity and anatomical localization, and also because, the methods for isolation and characterization are usually time consuming and have some technical limitations.ResultsIn this study, we describe a resource and method for obtaining immortalized cells with NSC characteristics obtained from mouse brain embryo.ConclusionsBecause these cells can be maintained indefinitely in culture, they may constitute a permanent source of NSC that can be used for research studies on neural development and regeneration.