Inhibitory pathways and the inhibition of luteinizing hormone-releasing hormone release by alcohol

Citation
A. Lomniczi et al., Inhibitory pathways and the inhibition of luteinizing hormone-releasing hormone release by alcohol, P NAS US, 97(5), 2000, pp. 2337-2342
Citations number
23
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN journal
00278424 → ACNP
Volume
97
Issue
5
Year of publication
2000
Pages
2337 - 2342
Database
ISI
SICI code
0027-8424(20000229)97:5<2337:IPATIO>2.0.ZU;2-D
Abstract
In this research we examined the mechanisms by which ethanol (EtOH) inhibit s luteinizing hormone-releasing hormone (LHRH) release from incubated media l basal hypothalamic explants. EtOH (100 mM) stimulated the release of two inhibitory neurotransmitters: gamma-aminobutyric acid (GABA) and beta-endor phin. EtOH also inhibited NO production, indicative of a suppression of nit ric oxide synthase (NOS) activity. This inhibition was reversed by naltroxo ne (10(-8) M), a mu-opioid receptor blocker, indicating that the inhibition of NOS by ROH is mediated by beta-endorphin, EtOH also blocked N-methyl-D- aspartic acid-induced LHRH release, but the blockade could not be reversed by either the GABA receptor blocker, bicuculline (10(-5) M), naltroxone (10 (-8) M), or both inhibitors added together. However, increasing the concent ration of naltrexone (10(-6) M) but not bicuculline (10(-4) M) reversed the inhibition, When we lowered the concentration of EtOH (50 mM), the EtOH-in duced blockade of LHRH release could be reversed by either bicuculline (10( -5) M), naltroxone (10(-8) M), or the combination of the two blockers. Ther efore, GABA is partially responsible for the blockade of N-methyl-D-asparti c acid-induced LHRH release, The block by GABA was exerted by inhibiting th e activation of cyclooxygenase by NO, because it was reversed by prostaglan din E-2, the product of activation of cyclooxygenase, Because the inhibitio n caused by the higher concentration of EtOH could not be reduced by bicucu lline (10(-4) M) but was blocked by naltroxone (10(-6) M), the action of al cohol can be accounted for by stimulation of beta-endorphin neurons that in hibit LHRH release by inhibition of activation of NOS and stimulation of GA BA release.