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
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.