PMID- 8625925
OWN - NLM
STAT- MEDLINE
DCOM- 19960621
LR  - 20131121
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 137
IP  - 4
DP  - 1996 Apr
TI  - The N-methyl-D-aspartate-mediated inhibitory control of gonadotropin-releasing 
      hormone release in the hypothalamus of the adult male guinea pig is expressed 
      through opioidergic systems.
PG  - 1468-73
AB  - Previously, we reported on a dual role of N-methyl-D-aspartate (NMDA) 
      receptor-mediated neurotransmission in the control of GnRH secretion from the 
      medial basal hypothalamus (MBH) of the adult male guinea pig, with a 
      predominantly inhibitory action in the intact animal, which is reversed to a 
      facilitatory role by orchidectomy. In the present study we examined the 
      hypothesis that endogenous opioids are involved in the NMDA receptor-mediated 
      inhibition of GnRH release. A static incubation system was used to test the 
      effects of excitatory amino acid agonists and an excitatory amino acid 
      antagonist, alone or in the presence of either the opiate agonist morphine or the 
      mu-receptor antagonist naloxone, on in vitro GnRH release from the isolated MBH 
      of intact, orchidectomized, or sham-operated guinea pigs. GnRH output from the 
      MBH of intact guinea pigs was markedly suppressed in the presence of the 
      NMDA-specific receptor agonist, N-methyl-D,L-aspartic acid (NMA; 50 mM), whereas 
      NMDA-specific receptor blockade with D,L-amino-5-phosphonovaleric acid (AP-5; 1 
      mM) resulted in a pronounced facilitation of GnRH release, as did exposure to the 
      non-NMDA-specific receptor agonist, kainic acid (50 mM). Opioidergic blockade 
      with naloxone (1 mM) caused a reversal of the responses to NMA and AP-5, with 
      exposure to these compounds this time resulting in clear facilitation and 
      inhibition, respectively. The stimulatory action of kainic acid, on the other 
      hand, remained unaffected by the presence of naloxone. Morphine inhibited basal 
      GnRH output and also annulled the stimulatory effect of AP-5 on GnRH secretion. 
      The results obtained from MBHs of sham-operated guinea pigs were identical to 
      those seen for the intact animals, with naloxone effectively increasing baseline 
      GnRH release and reversing the inhibitory effect of NMA and stimulatory action of 
      AP-5 on GnRH secretion to a facilitation and inhibition, respectively. On the 
      other hand, NMA caused a marked stimulation, whereas AP-5 produced a significant 
      inhibition of GnRH release from the MBHs of orchidectomized guinea pigs; neither 
      of these effects was altered by the presence of naloxone, which, moreover, had 
      only a marginal effect on basal GnRH output in this group of animals. In 
      conclusion, our present data provide evidence to support the view that the 
      primary inhibitory action of NMDA receptor-mediated neurotransmission on GnRH 
      release in the MBH of the intact male guinea pig is the result of activation of 
      opioidergic systems and that a marked reduction of opioid tone after orchidectomy 
      brings a facilitatory NMDA receptor-mediated system to the fore. On the other 
      hand, non-NMDA-specific kainate receptor-mediated facilitation of GnRH, 
      previously shown to be unaffected by gonadal status, appears to be also 
      independent from opioidergic modulation.
FAU - Giri, M
AU  - Giri M
AD  - Department of Endocrinology, University Hospital Ghent, Belgium.
FAU - Gao, C
AU  - Gao C
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 (Endorphins)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
RN  - 36B82AMQ7N (Naloxone)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - 76726-92-6 (2-Amino-5-phosphonovalerate)
SB  - IM
MH  - 2-Amino-5-phosphonovalerate/pharmacology
MH  - Animals
MH  - Endorphins/*physiology
MH  - Gonadotropin-Releasing Hormone/*antagonists & inhibitors/metabolism
MH  - Guinea Pigs
MH  - Hypothalamus/*metabolism
MH  - Hypothalamus, Middle/metabolism
MH  - Male
MH  - N-Methylaspartate/pharmacology/*physiology
MH  - Naloxone/pharmacology
MH  - Orchiectomy
MH  - Sex Factors
EDAT- 1996/04/01 00:00
MHDA- 1996/04/01 00:01
CRDT- 1996/04/01 00:00
PHST- 1996/04/01 00:00 [pubmed]
PHST- 1996/04/01 00:01 [medline]
PHST- 1996/04/01 00:00 [entrez]
AID - 10.1210/endo.137.4.8625925 [doi]
PST - ppublish
SO  - Endocrinology. 1996 Apr;137(4):1468-73. doi: 10.1210/endo.137.4.8625925.