PMID- 7750461
OWN - NLM
STAT- MEDLINE
DCOM- 19950619
LR  - 20181130
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 136
IP  - 6
DP  - 1995 Jun
TI  - Involvement of neuroexcitatory amino acids in the control of 
      gonadotropin-releasing hormone release from the hypothalamus of the adult male 
      guinea pig: predominantly inhibitory action of N-methyl-D-aspartate-mediated 
      neurotransmission and its reversal after orchidectomy.
PG  - 2404-7
AB  - Excitatory amino acids (EAA) have been implicated in the control of LH secretion 
      through facilitation of GnRH release, although disparate findings of an 
      inhibitory effect of EAA on LH secretion in several species after gonadectomy 
      have been reported. Using a static incubation system, we studied the effects of 
      EAA receptor agonists and antagonists on in vitro GnRH release from the isolated 
      medial basal hypothalamus (MBH) of the male guinea pig. In the presence of 0.4 mM 
      glycine, the N-methyl-D-aspartate (NMDA)-specific receptor agonist 
      N-methyl-D,L-aspartic acid (NMA) exerted a dose-dependent inhibition of GnRH 
      output from the MBH of intact guinea pigs, which was significant (P < or = 0.01) 
      at concentrations of 1 and 50 mM. The NMDA-specific receptor antagonist 
      D,L-2-amino-5-phosphonovaleric acid (AP-5) significantly stimulated GnRH release 
      at 10(-3) and 1 mM (P < or = 0.001) and was ineffective at 10(-6) mM. NMA (50 mM) 
      and AP-5 (1 mM) produced similar effects when tested at a lower glycine 
      concentration of 10 nM. The presence of the two compounds together resulted in 
      overall unchanged GnRH output. The inhibitory effect of 50 mM NMA was also 
      effectively blocked in the presence of 2 mM Mg2+ at both high and low glycine 
      concentrations. When, for comparative purposes, isolated MBHs of 50-day-old 
      intact male rats were exposed to 50 mM NMA, a response opposite to that seen in 
      the intact guinea pig was observed, with a marked increase in GnRH output (P < or 
      = 0.001). When tested at 10 nM glycine, 50 mM kainic acid, a non-NMDA-specific 
      receptor agonist, on the other hand, had a marked stimulatory effect on GnRH 
      output (P < or = 0.01) from intact guinea pig MBHs, an action that was prevented 
      in the presence of the kainate/quisqualate receptor antagonist 
      6,7-dinitro-quinoxaline-2,3-dione (0.1 mM); 6,7-dinitro-quinoxaline-2,3-dione 
      alone inhibited GnRH release (P < or = 0.01). In a separate series of 
      experiments, the effects of EAA (in the presence of 10 nM glycine) on GnRH 
      release from the MBHs of long term orchidectomized and sham-operated guinea pigs 
      were compared. Orchidectomy led to a dramatic reversal of the NMDA-mediated 
      inhibition of GnRH secretion observed in MBHs of sham-operated animals, with 50 
      mM NMA producing a marked increase (P < or = 0.0001) and 1 mM AP-5 resulting in a 
      clear inhibition (P < or = 0.0001) of GnRH release. Kainic acid (50 mM), on the 
      other hand, had a similar stimulatory action on GnRH release from the MBHs of 
      both orchidectomized (P < or = 0.0001) and sham-castrated (P < or = 0.001) guinea 
      pigs.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Giri, M
AU  - Giri M
AD  - Department of Endocrinology, University Hospital, Ghent, Belgium.
FAU - Kaufman, J M
AU  - Kaufman JM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Excitatory Amino Acids)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
RN  - 6384-92-5 (N-Methylaspartate)
SB  - IM
MH  - Animals
MH  - Excitatory Amino Acids/*physiology
MH  - Gonadotropin-Releasing Hormone/*metabolism
MH  - Guinea Pigs
MH  - Hypothalamus/drug effects/*metabolism/physiology
MH  - In Vitro Techniques
MH  - Male
MH  - N-Methylaspartate/pharmacology/*physiology
MH  - Orchiectomy
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, N-Methyl-D-Aspartate/agonists/antagonists & inhibitors/physiology
MH  - Synaptic Transmission/drug effects/*physiology
MH  - Testis/physiology
EDAT- 1995/06/01 00:00
MHDA- 1995/06/01 00:01
CRDT- 1995/06/01 00:00
PHST- 1995/06/01 00:00 [pubmed]
PHST- 1995/06/01 00:01 [medline]
PHST- 1995/06/01 00:00 [entrez]
AID - 10.1210/endo.136.6.7750461 [doi]
PST - ppublish
SO  - Endocrinology. 1995 Jun;136(6):2404-7. doi: 10.1210/endo.136.6.7750461.