beta-Endorphin blocks luteinizing hormone-releasing hormone release by inhibiting the nitricoxidergic pathway controlling its release.
beta-Endorphin blocks release of luteinizing hormone (LH)-releasing hormone (LHRH) into the hypophyseal portal vessels by stimulating mu-opiate receptors, thereby inhibiting secretion of LH. LHRH release is controlled by release of nitric oxide from nitricoxidergic (NOergic) neurons in the basal tuberal hypothalamus. To determine whether beta-endorphin exerts its inhibitory action on this NOergic pathway, medial basal hypothalami (MBH) from male rats were incubated with beta-endorphin (10(-8) M). beta-Endorphin decreased basal secretion of LHRH, and significantly inhibited the release of prostaglandin E2 (PGE2), a known stimulant of LHRH release. Incubation of MBH with beta-endorphin at various concentrations (10(-9)-10(-6) M) in vitro decreased the activity of NO synthase (NOS) (measured by the conversion of [14C]arginine to labeled citrulline). Conversely, the activity of NOS was increased by the mu-receptor antagonist, naltrexone (10(-8) M). Not only was the inhibitory action of beta-endorphin on LHRH and PGE2 release blocked by naltrexone (10(-8) M), but it increased NOS activity and LHRH and PGE2 release. beta-Endorphin also stimulated gamma-aminobutyric acid (GABA) release. Because GABA inhibits both nitroprusside (NP-induced PGE2 and LHRH release by blocking the activation of cyclooxygenase by NO, this is another mechanism by which beta-endorphin inhibits NP-induced PGE2 and LHRH release. The results indicate that beta-endorphin stimulates mu-opioid receptors on NOergic neurons to inhibit the activation and consequent synthesis of NOS in the MBH. beta-Endorphin also blocks the action of NO on PGE2 release and, consequently, on LHRH release, by stimulating GABAergic inhibitory input to LHRH terminals that blocks NO-induced activation of cyclooxygenase and consequent PGE2 secretion.
Faletti
A G
AG
Centro de Estudios Farmacologios y Botanicos, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Serrano 665, (1414) Buenos Aires, Argentina.
Mastronardi
C A
CA
Lomniczi
A
A
Seilicovich
A
A
Gimeno
M
M
McCann
S M
SM
Rettori
V
V
D000818:Animals; D015232:Dinoprostone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D007033:Hypothalamus, Middle / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008959:Models, Neurological; D009271:Naltrexone / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009924:Organ Culture Techniques; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000502:physiology*; D001615:beta-Endorphin / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology