Regulation of growth hormone (GH) secretion by different glutamate receptor subtypes in the rat

It has been firmly established that excitatory amino acids (EAAs), such as glutamate, are pivotal elements in the hypothalamic circuitry involved in the control of pituitary function. The actions of EAAs are mediated by different postsynaptic receptor subtypes, which include N-methyl D-aspartate (NMDA), kainate (KA), 2-amino-3-hydroxy-5 methyl-4-isoxazol propionic acid (AMPA) and metabotropic receptors. In this review, we summarize our 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. In addition, evaluation of the role of hypothalamic GH-releasing hormone (GHRH) in the stimulatory action of NMDA by means of immunoneutralization of endogenous GHRH or destruction of GHRH producing neurons suggested the involvement of signals other than GHRH in this response. Further, evidence was obtained on the modulation of the EAA system by gonadal factors, and on the physiological relevance of EAA pathways in the regulation of pulsatile GH release. 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.