PMID- 8156903
OWN - NLM
STAT- MEDLINE
DCOM- 19940516
LR  - 20131121
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 134
IP  - 5
DP  - 1994 May
TI  - Regulation of gonadotropin-releasing hormone gene expression by the excitatory 
      amino acids kainic acid and N-methyl-D,L-aspartate in the male rat.
PG  - 2026-31
AB  - The glutamate analogs N-methyl-D,L-aspartate (NMA) and kainic acid are involved 
      in the regulation of GnRH and LH release in mammals. It has recently been 
      reported that the increase in GnRH release induced by NMA is accompanied by an 
      increase in GnRH mRNA levels, as measured by in situ hybridization. In the 
      present study we assessed the effects of NMA and kainic acid on cytoplasmic mRNA 
      levels using the more quantitative solution hybridization/RNase protection assay. 
      To address the mechanism responsible for these mRNA changes, we also examined 
      changes in heteronuclear RNA transcripts as a reflection of gene transcription. 
      Adult male rats were implanted with a jugular catheter, and 1-2 days later, NMA 
      (14 mg/kg BW), kainic acid (2 mg/kg BW), both NMA and kainic acid, or saline 
      vehicle were injected through the cannula. Rats were killed 15 min or 1 h later 
      by decapitation, blood samples were collected for RIA of LH, brains were removed, 
      and the preoptic area was dissected and frozen. Cytoplasmic and nuclear RNA were 
      extracted and assayed separately by RNase protection assay. Treatment with NMA or 
      NMA plus kainic acid resulted in significantly elevated cytoplasmic mRNA levels 
      15 min and 1 h later compared to saline control values, with no differences 
      between the two drug treatments observed. Kainic acid stimulated mRNA levels 1 h, 
      but not 15 min after injection. Nuclear RNA transcripts were unaffected by all 
      drug or vehicle treatments. As nuclear primary transcript levels presumably 
      reflect GnRH gene transcription, and these levels are unaltered, the present 
      study indicates that the regulation of GnRH gene expression by excitatory amino 
      acids occurs at a posttranscriptional level. The increase in cytoplasmic GnRH 
      mRNA levels also does not result from an increased translocation of the 
      relatively large nuclear GnRH mRNA pool into the cytoplasm, because nuclear GnRH 
      mRNA levels are also unchanged. Therefore, the elevation of cytoplasmic mRNA 
      levels after excitatory amino acid treatment is probably due to an increase in 
      mRNA stability.
FAU - Gore, A C
AU  - Gore AC
AD  - Dr. Arthur M. Fishberg Research Center in Neurobiology, Mt. Sinai School of 
      Medicine, City University of New York, New York 10029.
FAU - Roberts, J L
AU  - Roberts JL
LA  - eng
GR  - DK-08743/DK/NIDDK NIH HHS/United States
GR  - DK-39029/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (RNA, Heterogeneous Nuclear)
RN  - 0 (RNA, Messenger)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - 9002-67-9 (Luteinizing Hormone)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - Animals
MH  - Cell Nucleus/metabolism
MH  - Cytoplasm/metabolism
MH  - Gene Expression Regulation/*drug effects
MH  - Gonadotropin-Releasing Hormone/*genetics
MH  - Kainic Acid/*pharmacology
MH  - Luteinizing Hormone/blood
MH  - Male
MH  - N-Methylaspartate/*pharmacology
MH  - RNA, Heterogeneous Nuclear/metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 1994/05/01 00:00
MHDA- 1994/05/01 00:01
CRDT- 1994/05/01 00:00
PHST- 1994/05/01 00:00 [pubmed]
PHST- 1994/05/01 00:01 [medline]
PHST- 1994/05/01 00:00 [entrez]
AID - 10.1210/endo.134.5.8156903 [doi]
PST - ppublish
SO  - Endocrinology. 1994 May;134(5):2026-31. doi: 10.1210/endo.134.5.8156903.