Role of excitatory amino acids in the control of growth hormone secretion.

Excitatory amino acids (EEAs), such as glutamate, are pivotal elements in the hypothalamic circuitry involved in the control of pituitary function. The actions of EEAs are mediated by different postsynaptic receptor subtypes, which include the ionotropic receptors N-methyl-D-aspartate (NMDA), kainate (KA), 2-amino-3-hydroxy- 5 methyl-4-isoxazol propionic acid (AMPA), as well as metabotropic receptors. In this review, we summarize the experimental work on the role of EAA neurotransmission in the control of GH secretion in the rat. Detailed characterization of the effects of agonists and antagonists of glutamate receptors on GH release revealed that activation of NMDA, KA, and AMPA receptors at different age-points resulted in clear-cut stimulation of GH secretion, although age- and sex-dependent differences were detected in the pattern of response to the different agonists. This stimulatory action was proven nitric oxide (NO)-dependent and not exerted at the pituitary level. Moreover, the effects of NMDA on GH release likely involve additional mediators other than hypothalamic GH-releasing hormone (GHRH). In contrast, the role of metabotropic receptors seems to be marginal, and only inhibitory actions were observed after activation of different receptor subtypes. Furthermore, evidence was obtained on the modulation of the EEA system by gonadal factors in the control of GH secretion, and on the physiological relevance of EEA pathways in the regulation of pulsatile GH release. The analysis of interactions between EAA receptors and other neuronal pathways evidenced the close interactions between different systems involved in the control of GH secretion. Blockade of glutamate receptors abolished the stimulatory effect of GABA and ghrelin on GH secretion and, inversely, blockade of ghrelin or GABA receptors abolished the stimulatory effect of EAAs. In conclusion, our data using the rat as animal model provide evidence for a pivotal role of glutamate pathways in the regulation of GH secretion throughout the life-span.