TY - JOUR
T1 - β-Endorphin blocks luteinizing hormone-releasing hormone release by inhibiting the nitricoxidergic pathway controlling its release
AU - Faletti, Alicia G.
AU - Mastronardi, Claudio A.
AU - Lomniczi, Alejandro
AU - Seilicovich, Adriana
AU - Gimeno, Martha
AU - Mccann, Samuel M.
AU - Rettori, Valeria
PY - 1999/2/16
Y1 - 1999/2/16
N2 - β-Endorphin blocks release of luteinizing hormone (LH)-releasing hormone (LHRH) into the hypophyseal portal vessels by stimulating μ-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 β-endorphin exerts its inhibitory action on this NOergic pathway, medial basal hypothalami (MBH) from male rats were incubated with β-endorphin (10-8 M). β-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 β- 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 μ-receptor antagonist, naltrexone (10-8 M). Not only was the inhibitory action of β-endorphin on LHRH and PGE2 release blocked by naltrexone (10- 8 M), but it increased NOS activity and LHRH and PGE2 release. β-Endorphin also stimulated γ-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 β- endorphin inhibits NP-induced PGE2 and LHRH release. The results indicate that β-endorphin stimulates μ-opioid receptors on NOergic neurons to inhibit the activation and consequent synthesis of NOS in the MBH. β- 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.
AB - β-Endorphin blocks release of luteinizing hormone (LH)-releasing hormone (LHRH) into the hypophyseal portal vessels by stimulating μ-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 β-endorphin exerts its inhibitory action on this NOergic pathway, medial basal hypothalami (MBH) from male rats were incubated with β-endorphin (10-8 M). β-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 β- 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 μ-receptor antagonist, naltrexone (10-8 M). Not only was the inhibitory action of β-endorphin on LHRH and PGE2 release blocked by naltrexone (10- 8 M), but it increased NOS activity and LHRH and PGE2 release. β-Endorphin also stimulated γ-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 β- endorphin inhibits NP-induced PGE2 and LHRH release. The results indicate that β-endorphin stimulates μ-opioid receptors on NOergic neurons to inhibit the activation and consequent synthesis of NOS in the MBH. β- 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.
KW - Cyclooxygenase
KW - Naltrexone
KW - Nitric oxide synthase
KW - Prostaglandin E
KW - μ-Opiate receptor
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U2 - 10.1073/pnas.96.4.1722
DO - 10.1073/pnas.96.4.1722
M3 - Article
C2 - 9990091
AN - SCOPUS:0033573916
SN - 0027-8424
VL - 96
SP - 1722
EP - 1726
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 4
ER -