Surging interest on how growth hormone (GH) affects the central nervous system (CNS) is apparent over the latest decades. Various clinics and basic science laboratories suggest important function of GH for many behavioural aspects.1-3 New light is shed on GHs influence on cognitive functions by Martin‐Rodriguez and co‐workers in the present volume of Acta Physiologica by implementing ground‐breaking methodology.4 They use a specific cell line model to examine effects of chronic GH and its mediator insulin‐like growth factor‐1 (IGF‐I) hyper‐secretion on instrumental learning. The latter is linked to the prefrontal cortex, related circuits and on long‐term potentiation (LTP) evoked in hippocampal synapses. What is more, the authors expand their study to neurogenesis in dentate nucleus of hippocampus4. The model used in this study allows them to move research on knowledge on GH and its effects on brain function a significant step further.

It is well established that GH mediates most of its effects by releasing IGF‐1 through stimulation of GH receptors (GHR), in particular in the liver, but GH may also release its mediator in the brain. Both GH and IGF‐1 are known to cross the blood‐brain barrier (BBB) and affect specific targets for these hormones in a variety of brain regions. These include areas related to cognitive function as hippocampus.1, 2 The discovery of GH and IGF‐1 receptors in the CNS and their distribution in brain areas associated with the functional anatomy of behavioural effects induced by activation of the somatotrophic axis (GH/IGF‐1 axis) has brought up new aspects on the mechanisms underlying beneficial behavioural effects seen for the two hormones.1, 3

In individuals with deficient GH production, which may result from disturbed function of the GH/IGF‐1 axis, a reduction in several dimensions related to quality of life (QOL) is observed. Impaired activity in this axis may appear as a result of various types of pathology, but also from normal aging processes. In patients with a pathological decline in circulating GH, however, exogenous compensation of the hormone has been seen to counteract these QOL‐disabilities.1, 5

In fact, a number of clinical studies have suggested that GH replacement can improve the psychological capabilities in adult GH‐deficient (GHD) patients. Profound effects of the hormone on certain functions, including memory and learning, mental alertness, motor skills, motivation and working capacity have thus been reported.1, 5 Also in GHD children the hormone replacement has been shown to produce significant improvement in many behavioural problems seen in these individuals. Furthermore, the GH/IGF‐1‐axis is implicated in prenatal and postnatal phases of brain development, including neurogenesis, neuronal differentiation, synaptogenesis and restore cortical plasticity in adult life.6 Therefore, studies on effects of both GH and IGF‐1 on the brain function are of potential interest.

In the recent study by Martin‐Rodriguez and co‐workers, subcutaneous implantation of a GC cell line in male rats forming a growth hormone‐secreting tumour induces a controllable over‐secretion of GH followed by elevated IGF‐I levels, a procedure allowing for studies on short‐term effects of these hormones on brain function. The authors used this cell line model with the ambition to explore effects of chronic GH/IGF‐I hyper‐secretion in adult male rats on instrumental learning linked to prefrontal and related circuits and on LTP evoked in hippocampal synapses in behaving animals as well as neurogenesis in dentate nucleus.

Thus, using Wistar Furth rats implanted with the GC cell line the authors have studied effects on associative learning, long‐term memories, LTP and neurogenesis of GH hyper‐secretion, as well as those following surgical resection of the tumour. They found that evoked LTP in the hippocampus was larger and lasted longer in rats bearing tumours than in control groups. It was concluded that hyper‐secretion of GH/IGF‐1 plays a positive role in maintaining long‐term plastic changes in certain hippocampal synapses indicating a function in memory‐related properties of this brain areas.4

However, in contrast to some earlier reported data6 their studies on the effects of hyper‐secretion of the actual hormones on neurogenesis no increase in the number of newly generated neurons was seen. This is also in contrast to our recent observation that high concentrations of GH may stimulate neurite outgrowth in rat hippocampal cells.7 On the other hand, after applying additional approaches for their investigation on neurogenesis Martin‐Rodriguez and co‐workers noted that hyper‐secretion of GH and IGF‐I might cause a premature acceleration of early progenitors to promote neuronal differentiation.4 Also, the increase in GH and its mediator IGF‐I was suggested to accelerate the intermediate phases of neurogenesis towards the maturation of newborn neurons into mature granule cells.

Consequently, chronic adult‐onset of GH/IGF‐I hyper‐secretion was found to cause a stimulation of neural differentiation, but also maturation, and integration in hippocampal areas. From their finding Martin‐Rodriguez and co‐workers realized that adult‐onset of hyper‐secretion of GH and its mediator IGF‐I improve neurocognitive functions, long‐term memories, LTP, as well as neural differentiation, migration and maturation. They emphasized the potential of stimulating neurogenesis to enhance cognitive functions and a potential role of GH in modulating memory, cognition, behaviour and neurogenesis in normal and as well as abnormal states of this hormone.

In summary, the paper of Martin‐Rodriguez and co‐workers4 provides new and interesting findings regarding the action of GH on cognitive capabilities, that extends previously published data by these authors but also by other investigators working in the same field. Their paper describes some new and highly qualified approaches for studies on important functions in the brain involving the GH/IGF‐1 axis. Also, in addition to the hormone hyper‐secreting cell‐line it includes several behavioural assays, which strengthened the possibility to understand the capacity of GH to modulate important functions in the CNS, as previously implicated for the hormone. The use of these methods will certainly promote and allow for forthcoming studies related to the issue of the GH/IGF‐1 axis and its potential action on many vital functions in the brain including those of learning and memory.

在最近的几十年中，人们对生长激素（GH）如何影响中枢神经系统（CNS）的兴趣激增。各种诊所和基础科学实验室都建议GH在许多行为方面具有重要作用。1-3在当前《生理学报》中，通过实施突破性的方法，Martin-Rodriguez及其同事对GHs对认知功能的影响有了新的揭示。4他们使用特定的细胞系模型来检查慢性GH及其介导的胰岛素样生长因子-1（IGF-1）过度分泌对仪器学习的影响。后者与前额叶皮层，相关回路以及海马突触中诱发的长期增强（LTP）有关。而且，作者将研究范围扩展到海马4齿状核中的神经发生。该研究中使用的模型使他们能够将有关GH及其对脑功能的影响的研究进一步向前迈进了一大步。

众所周知，GH可以通过刺激GH受体（GHR）释放IGF-1来介导其大部分作用，尤其是在肝脏中，但是GH也可以在大脑中释放其介体。已知GH和IGF-1都跨越血脑屏障（BBB），并影响大脑各个区域中这些激素的特定靶标。这些包括与认知功能有关的海马区。1，2在中枢神经系统中发现GH和IGF-1受体以及它们在脑区的分布与激活营养轴（GH / IGF-1轴）引起的行为效应的功能解剖相关，这为研究带来了新的方面。两种激素的有益行为效应的潜在机制。一三

在GH产生不足的个体中，这可能是由于GH / IGF-1轴的功能受干扰所致，观察到与生活质量（QOL）相关的几个方面的降低。该轴活动性受损可能是各种病理类型的结果，也是正常衰老过程的结果。然而，在循环GH病理性下降的患者中，已发现激素的外源性补偿可以抵消这些QOL残疾。1、5

实际上，许多临床研究表明，GH替代可以改善成人GH缺乏（GHD）患者的心理能力。因此，已经报道了激素对某些功能的深远影响，包括记忆和学习，心理警觉，运动技能，动机和工作能力。1，5同样，在GHD儿童中，激素替代已显示出在这些人所见的许多行为问题上产生了显着改善。此外，GH / IGF-1轴与大脑发育的产前和产后阶段有关，包括成年期的神经发生，神经元分化，突触形成和恢复皮层可塑性。6 因此，有关GH和IGF-1对脑功能的影响的研究可能引起人们的兴趣。

在Martin‐Rodriguez及其同事的最新研究中，在形成生长激素分泌型肿瘤的雄性大鼠中皮下植入GC细胞系可诱导GH的可控过度分泌，然后升高IGF-I水平，该方法可这些激素对脑功能的短期影响的研究。作者使用这种细胞系模型来探索成年雄性大鼠慢性GH / IGF-I超分泌对与前额叶和相关回路相关的工具学习以及行为动物海马突触诱发的LTP以及神经发生的影响。在齿状核中。

因此，作者使用植入了GC细胞系的Wistar Furth大鼠，研究了其对联想学习，长期记忆，LTP和GH过度分泌的神经发生以及外科手术切除肿瘤后的影响。他们发现，荷瘤大鼠的海马中诱发的LTP比对照组更大，并且持续时间更长。结论是，GH / IGF-1的高分泌在维持某些海马突触的长期塑性变化中起积极作用，表明该脑区域的记忆相关特性起作用。4

然而，相对于一些先前报道的数据6项它们对神经发生的实际激素在新生成的神经元的数量没有增加的过度分泌的影响研究中看到。这也与我们最近的观察相反，我们的观察表明高浓度的GH可能刺激大鼠海马细胞中的神经突生长。7另一方面，在应用其他方法进行神经发生研究后，Martin-Rodriguez及其同事指出，GH和IGF-I的过度分泌可能会导致早期祖细胞过早加速，从而促进神经元分化。4 此外，GH及其介体IGF-I的增加也被认为可加速神经发生的中间阶段，从而使新生神经元成熟为成熟的颗粒细胞。

因此，发现成年的GH / IGF-I过度分泌的慢性发作可刺激神经分化，并促进海马区的成熟和整合。从他们的发现中，Martin-Rodriguez及其同事认识到，成年后GH过度分泌及其介体IGF-I改善了神经认知功能，长期记忆，LTP以及神经分化，迁移和成熟。他们强调了刺激神经发生以增强认知功能的潜力，以及GH在调节该激素正常和异常状态下的记忆，认知，行为和神经发生中的潜在作用。

总而言之，马丁·罗德里格斯（Martin‐Rodriguez）和同事的论文4提供了有关GH对认知功能的作用的新的有趣发现，这些发现扩展了这些作者以及同一领域其他研究人员先前发表的数据。他们的论文描述了一些新的高质量方法，用于研究涉及GH / IGF-1轴的大脑重要功能。此外，除了激素分泌过多的细胞系外，它还包括多种行为检测，这增强了了解GH调节CNS中重要功能的能力的可能性，这与以前涉及的激素有关。这些方法的使用肯定会促进并允许进行有关GH / IGF-1轴问题及其对大脑许多重要功能（包括学习和记忆功能）的潜在作用的研究。