Growing knowledge: How growth hormone improves learning

This is the authors' abstract. We don't add key points for this paper.

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. The authors declare no conflict of interest.