Growth hormone overexpression generates an unfavorable phenotype in juvenile transgenic zebrafish under hypoxic conditions

Growth hormone (GH) has numerous functions in different organisms. A recently described function for GH is its role in protecting against damage caused by a decrease in oxygen levels. To evaluate the effects of GH-transgenesis on hypoxia tolerance, we used a GH-transgenic zebrafish model. We found that the transgenic fish have higher mortality rates when exposed to low oxygen levels (1.5 mg O₂L(-1)) for 24 h. The lower capacity of GH-transgenic fish to manage a hypoxic environment was investigated by analyzing different metabolic and molecular factors. The transgenic fish showed increased oxygen consumption, which confirms the larger oxygen demand imposed by transgenesis. At the gene expression level, transgenesis increased lactate dehydrogenase (LDH) and creatine kinase muscle (CKM) expression in fish under normoxic conditions. This result suggests that excessive GH expression stimulates the synthesis of enzymes involved in anaerobic metabolism. Conversely, the interaction between transgenesis and hypoxia caused an increased expression of hemoglobin (Hb), hypoxia-inducible factor (HIF1a) and prolyl-4-hydroxylase (PHD) genes. Additionally, GH-transgenesis increased LDH activity and increased lactate content. Taken together, these findings indicate that GH-transgenesis impaired the ability of juvenile zebrafish to sustain an aerobic metabolism and induced anaerobic metabolism when the fish were challenged with low oxygen levels.