Glutamate: a major excitatory transmitter in neuroendocrine regulation.
Brann DW
Department of Physiology and Endocrinology, Medical College of Georgia,
Augusta 30912.
Neuroendocrinology, 61(3):213-25 1995 Mar
Excitatory amino acids (EAAs), such as glutamate and aspartate, are found in
large concentrations in presynaptic boutons of a variety of important
hypothalamic nuclei, including the arcuate nucleus, supraoptic nucleus,
suprachiasmatic nucleus, paraventricular nucleus, organum vasculosa of the
lamina terminalis (OVLT) and preoptic area (POA). Likewise, the different
ionotropic/metabotropic EAA receptor subtypes are found in the same regions
of the hypothalamus although there are differences 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 anterior lobe, intermediate lobe and
posterior lobe of the pituitary. The majority of work to date has focused on
the role of EAAs in the control of LH secretion. Administration of
glutamate, NMDA, kainate or AMPA leads to rapid LH release mediated through
the stimulation of hypothalamic GnRH release. The major site of NMDA action
appears to be the OVLT/preoptic area--where GnRH cell bodies reside, whereas
AMPA and kainate have been suggested to act primarily at the arcuate
nucleus/median eminence--the site of GnRH nerve terminals. There is evidence
that some of the effects of glutamate on GnRH release may involve activation
of the novel neurotransmitter nitric oxide and possibly catecholamines. The
physiological importance of EAAs in the control of LH surge expression is
evidenced by the findings that the steroid-induced LH surge in
ovariectomized animals and the preovulatory LH surge in cycling animals and
in PMSG-primed animals is blocked by treatment with specific NMDA receptor
antagonists, or non-NMDA receptor antagonists. EAAs also appear to be
important in regulating the normal pulsatile pattern of 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 rat. A role for NMDA
receptors in the achievement of puberty has been suggested since activation
of NMDA receptors has been shown to advance the time of vaginal opening in
the immature female rat, while kainate and DNQX were without effect.
Steroids have been reported not to affect NMDA receptor binding in the
hypothalamus; however, steroids appear to up-regulate AMPA receptor GluR1
subunit levels and non-NMDA receptor binding in the hypothalamus. Steroids
also increase the release rates of glutamate and aspartate in the POA during
the steroid-induced LH surge in the ovariectomized adult rat.(ABSTRACT
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