Opioid-glutamate-nitric oxide connection in the regulation of luteinizing hormone secretion in the rat

Ganapathy K. Bhat, Virendra B. Mahesh, Lin Ping, Lynn Chorich, Vernon T. Wiedmeier, Darrell W Brann

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Opioid neurons are recognized to be an important component of the inhibitory 'brake' in the CNS that restrains LHRH secretion. Opioid inhibition could be exerted directly on LHRH neurons, or it could be achieved via indirect mechanisms involving restrainment of excitatory 'accelerator' neurons that facilitate LHRH release. The purpose of the present study was to explore the second hypothesis by investigating whether removal of opioid inhibition by administering the opioid antagonist, naloxone leads to enhanced activation of glutamate and nitric oxide (NO) neurons, which are known to be important excitatory 'accelerator' components for the control of LHRH secretion. Naloxone administration (2.5 mg/kg) to adult male rats induced a significant elevation of serum LH levels at 20 min post injection. NOS activity in preoptic area (POA) and medial basal hypothalamic (MBH) fragments was demonstrated to be significantly elevated 20 min post naloxone injection. Administration of a glutamate (NMDA) receptor antagonist (MK-801, 0.2 mg/kg) abolished the naloxone-induced increase in NOS activity in the POA and MBH, with a corresponding block of the naloxone-induced LH release. Glutamate appears to only be involved in LH surge generation and not to regulate basal LH levels, as MK-801 had no effect on basal LH release. Because previous work by our laboratory and others have provided evidence that NO is a mediator of glutamate effects in the hypothalamus, these findings are interpreted to mean that opioid inhibition is mediated on glutamate neurons that are upstream of NO neurons. In support of this contention, we found that NMDA treatment enhanced NOS activity in the male rat POA and MBH fragments in vitro, an effect that was specific as it was completely blocked by the NMDA receptor antagonist, MK-801. Additionally, in vivo microdialysis studies revealed that naloxone treatment significantly enhances glutamate release in the preoptic area (POA) at 15 min post injection in conscious, unanesthetized, freely moving male rats. Release rates of the control amino acid, serine did not change significantly following naloxone injection. Taken as a whole, these findings provide evidence for an opioid-glutamate-NO pathway in the control of LHRH secretion, and they demonstrate the importance of 'brake-accelerator' interactions in the control of LHRH and LH secretion.

Original languageEnglish (US)
Pages (from-to)955-960
Number of pages6
JournalEndocrinology
Volume139
Issue number3
DOIs
StatePublished - Jan 1 1998

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Naloxone
Luteinizing Hormone
Opioid Analgesics
Glutamic Acid
Gonadotropin-Releasing Hormone
Nitric Oxide
Preoptic Area
Neurons
Dizocilpine Maleate
Injections
N-Methyl-D-Aspartate Receptors
Excitatory Amino Acid Antagonists
Narcotic Antagonists
Microdialysis
N-Methylaspartate
Serine
Hypothalamus
Amino Acids
Therapeutics
Serum

ASJC Scopus subject areas

  • Endocrinology

Cite this

Opioid-glutamate-nitric oxide connection in the regulation of luteinizing hormone secretion in the rat. / Bhat, Ganapathy K.; Mahesh, Virendra B.; Ping, Lin; Chorich, Lynn; Wiedmeier, Vernon T.; Brann, Darrell W.

In: Endocrinology, Vol. 139, No. 3, 01.01.1998, p. 955-960.

Research output: Contribution to journalArticle

Bhat, Ganapathy K. ; Mahesh, Virendra B. ; Ping, Lin ; Chorich, Lynn ; Wiedmeier, Vernon T. ; Brann, Darrell W. / Opioid-glutamate-nitric oxide connection in the regulation of luteinizing hormone secretion in the rat. In: Endocrinology. 1998 ; Vol. 139, No. 3. pp. 955-960.
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