Excitatory amino acids (EAAs), such as glutamate and aspartate, are fo
und in large concentrations in presynaptic boutons of a variety of imp
ortant hypothalamic nuclei, including the arcuate nucleus, supraoptic
nucleus, suprachiasmatic nucleus, paraventricular nucleus, organum vas
culosa of the lamina terminalis (OVLT) and preoptic area (POA). Likewi
se, the different ionotropic/metabotropic EAA receptor subtypes are fo
und in the same regions of the hypothalamus although there are differe
nces in their individual patterns of localization. Furthermore, there
is evidence supporting the presence of ionotropic N-methyl-D-aspartate
(NMDA) receptors and non-NMDA (kainate and AMPA) receptors in the ant
erior lobe, intermediate lobe and posterior lobe of the pituitary. The
majority of work to date has focused on the role of EAAs in the contr
ol of LH secretion. Administration of glutamate, NMDA, kainate or AMPA
leads to rapid LH release mediated through the stimulation of hypotha
lamic GnRH release. The major site of NMDA action appears to be the OV
LT/preoptic area - where GnRH cell bodies reside, whereas AMPA and kai
nate have been suggested to act primarily at the arcuate nucleus/media
n eminence - the site of GnRH nerve terminals. There is evidence that
some of the effects of glutamate on GnRH release may involve activatio
n of the novel neurotransmitter nitric oxide and possibly catecholamin
es. The physiological importance of EAAs in the control of LH surge ex
pression is evidenced by the findings that the steroid-induced LH surg
e in ovariectomized animals and the preovulatory LH surge in cycling a
nimals and in PMSG-primed animals is blocked by treatment with specifi
c NMDA receptor antagonists, or non-NMDA receptor antagonists. EAAs al
so appear to be important in regulating the normal pulsatile pattern o
f LH release as evidenced by the finding that both the NMDA antagonist
, AP5, and the AMPA/kainate antagonist, DNQX, lower mean LH levels, LH
pulse amplitude and LH pulse frequency in the adult ovariectomized ra
t. A role for NMDA receptors in the achievement of puberty has been su
ggested since activation of NMDA receptors has been shown to advance t
he time of vaginal opening in the immature female rat, while kainate a
nd DNQX were without effect. Steroids have been reported not to affect
NMDA receptor binding in the hypothalamus; however, steroids appear t
o up-regulate AMPA receptor GluR(1) subunit levels and non-NMDA recept
or binding in the hypothalamus. Steroids also increase the release rat
es of glutamate and aspartate in the POA during the steroid-induced LH
surge in the ovariectomized adult rat. Evidence also exists supportin
g a role for EAAs in the release of other pituitary hormones such as A
CTH, growth hormones, prolactin, oxytocin and vasopressin which will a
lso be discussed. Taken as a whole, the studies described herein provi
de extensive and convincing evidence that EAA transmitters play a pivo
tal role in the neuroendocrine regulation of a variety of hormonal sys
tems.