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Aim: Besides their metabolic and endocrine functions, the growth hormone (GH) and its mediated factor, the insulin‐like growth factor I (IGF‐I), have been implicated in different brain functions, including neurogenesis. Long‐lasting elevated GH and IGF‐I levels result in non‐reversible somatic, endocrine and metabolic morbidities. However, the subcutaneous implantation of the GH‐secreting (GH‐S) GC cell line in rats leads to the controllable over‐secretion of GH and elevated IGF‐I levels, allowing the experimental study of their short‐term effects on brain functions. Methods: Adult rats were implanted with GC cells and checked 10 weeks later, when a GH/IGF‐I‐secreting tumour was already formed. Results: Tumour‐bearing rats acquired different operant conditioning tasks faster and better than controls and tumour‐resected groups. They also presented better retentions of long‐term memories in the passive avoidance test. Experimentally evoked long‐term potentiation (LTP) in the hippocampus was also larger and longer lasting in the tumour bearing than in the other groups. Chronic adult‐onset of GH/IGF‐I hypersecretion caused an acceleration of early progenitors, facilitating a faster neural differentiation, maturation and integration in the dentate gyrus, and increased the complexity of dendritic arbours and spine density of granule neurons. Conclusion: Thus, adult‐onset hypersecretion of GH/IGF‐I improves neurocognitive functions, long‐term memories, experimental LTP and neural differentiation, migration and maturation. [ABSTRACT FROM AUTHOR]

Thyroid hormones play an important morphogenetic role during the fetal and neonatal periods and regulate numerous metabolic processes. In the central nervous system, they control myelination and overall brain development, regional gene expression, and regulation of oxygen consumption. Their deficiency in the fetal and neonatal periods causes severe mental retardation, due to lack of thyroid function, or to iodine deficiency. At the same time, nitric oxide is an atypical neurotransmitter that also has special relevance in neuronal development and plasticity and functions as a vasodilator, regulating cerebral blood flow. Although under physiological conditions it functions as a neuroprotector, in excess it can be neurotoxic. We have studied, by immunocytochemical and Western blot techniques, the evolution of the expression of neuronal and inducible isoforms of the enzyme nitric oxide synthase, and of nitrotyrosine as a marker of protein nitration produced by the presence of nitric oxide, during the early stages of postnatal brain development. We induced hypothyroidism by administering mercaptomethylimidazole to pregnant mothers, from the seventh day of gestation until the sacrifice of the offspring. The results show a delay in the evolution of the expression of the two isoforms of the enzyme nitric oxide synthase in hypothyroid animals, followed by an anomalous overexpression in later stages. Finally, the expression of nitrotyrosine follows an evolution that is synchronized with that shown by both isoenzymes in control and hypothyroid animals., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)