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 recept ors, thereby inhibiting secretion of LH. LHRH release is controlled by rele ase of nitric oxide from nitricoxidergic (NOergic) neurons in the basal tub eral hypothalamus. To determine whether beta-endorphin exerts its inhibitor y action on this NOergic pathway, medial basal hypothalami (MBH) from male rats were incubated with beta-endorphin (10(-8) M). beta-Endorphin decrease d basal secretion of LHRH, and significantly inhibited the release of prost aglandin E-2 (PGE(2)), a known stimulant of LHRH release. Incubation of MBH with beta-endorphin at various concentrations (10(-9)-10(-6) M) in vitro d ecreased the activity of NO synthase (NOS) (measured by the conversion of [ C-14]arginine to labeled citrulline), Conversely, the activity of NOS was i ncreased by the mu-receptor antagonist, naltrexone (10(-8) M). Not only was the inhibitory action of beta-endorphin on LHRH and PGE(2) release blocked by naltrexone (10(-8) M), but it increased NOS activity and LHRH and PGE(2 ) release, beta-Endorphin also stimulated gamma-aminobutyric acid (GABA) re lease, Because GABA inhibits both nitroprusside (NP-induced PGE(2) and LHRH release by blacking the activation of cyclooxygenase by NO, this is anothe r mechanism by which beta-endorphin inhibits NP-induced PGE(2) and LHRH rel ease, The results indicate that beta-endorphin stimulates mu-opioid recepto rs on NOergic neurons to inhibit the activation and consequent synthesis of NOS in the MBH. beta-Endorphin also blocks the action of NO on PGE(2) rele ase and, consequently, on LHRH release, by stimulating GABAergic inhibitory input to LHRH terminals that blocks NO-induced activation of cyclooxygenas e and consequent PGE(2) secretion.