β-Endorphin blocks luteinizing hormone-releasing hormone release by inhibiting the nitricoxidergic pathway controlling its release

Abstract

ABSTRACT␤-Endorphin blocks release of luteinizing hormone (LH)-releasing hormone (LHRH) into the hypophyseal portal vessels by stimulating -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 ␤-endorphin exerts its inhibitory action on this NOergic pathway, medial basal hypothalami (MBH) from male rats were incubated with ␤-endorphin (10 ؊8 M). ␤-Endorphin decreased basal secretion of LHRH, and significantly inhibited the release of prostaglandin E 2 (PGE 2 ), a known stimulant of LHRH release. Incubation of MBH with ␤-endorphin at various concentrations (10 ؊9 -10 ؊6 M) in vitro decreased the activity of NO synthase (NOS) (measured by the conversion of [ 14 C]arginine to labeled citrulline). Conversely, the activity of NOS was increased by the -receptor antagonist, naltrexone (10 ؊8 M). Not only was the inhibitory action of ␤-endorphin on LHRH and PGE 2 release blocked by naltrexone (10 ؊8 M), but it increased NOS activity and LHRH and PGE 2 release. ␤-Endorphin also stimulated ␥-aminobutyric acid (GABA) release. Because GABA inhibits both nitroprusside (NPinduced PGE 2 and LHRH release by blocking the activation of cyclooxygenase by NO, this is another mechanism by which ␤-endorphin inhibits NP-induced PGE 2 and LHRH release. The results indicate that ␤-endorphin stimulates -opioid receptors on NOergic neurons to inhibit the activation and consequent synthesis of NOS in the MBH. ␤-Endorphin also blocks the action of NO on PGE 2 release and, consequently, on LHRH release, by stimulating GABAergic inhibitory input to LHRH terminals that blocks NO-induced activation of cyclooxygenase and consequent PGE 2 secretion.The endogenous opioid peptide, ␤-endorphin, plays an important role in inhibiting the release of luteinizing hormone (LH)-releasing hormone (LHRH) (1-3). Changes in release of ␤-endorphin within the hypothalamus are important in controlling the cyclic release of LHRH that induces the preovulatory surge of LH (3-5). Inhibitory opioid tone mediated by ␤-endorphin is removed in response to the increased plasma estrogen concentrations resulting from estrogen secretion by the preovulatory follicles, thereby facilitating the preovulatory release of LHRH. This tone maintains LHRH secretion at low levels during the rest of the estrous cycle of the rat and the menstrual cycle of monkeys (4). ␤-Endorphin acts mainly by activating -opioid receptors because -opioid receptor blockers such as naltrexone prevent its action (5).The mechanism by which ␤-endorphin inhibits LHRH release is not well understood. Recent evidence indicates that LHRH release is controlled primarily by nitricoxidergic (NOergic) neurons in the arcuate-median eminence region (6-9). The NO released from these neurons diffuses into the terminals of the LHRH neurons and activates not only guanylyl cyclase, leading to the release of cGMP, but also cyclooxygenase, leading to release of prostaglandins, i...

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

“…As shown previously the addition of GABA (10 mM) did not affect ␤-endorphin release from MBH (15). This result was confirmed in the current experiments (Fig.…”

“…Previous experiments demonstrated that incubation of MBH with ␤-endorphin (10 nM) significantly increased GABA release (15) and also that NO had a stimulatory effect (14). In the present experiments we found that EtOH (100 mM) significantly stimulated (P Ͻ 0.05) GABA release (Fig.…”

“…We previously have shown that ␤-endorphin inhibits LHRH release. Although ␤-endorphin activates GABA release, the released GABA appears to have no inhibitory effect on ␤-endorphin release, and GABA also does not directly affect the alteration of NOS activity (15). In the present experiments, we also have shown that NO released from NP appears to act back on the ␤-endorphin neurons to reduce secretion of ␤-endorphin.…”

“…Furthermore, ␤-endorphin also blocked the action of NP on PGE 2 release and consequently LHRH secretion (15).…”

Alcohol inhibits luteinizing hormone-releasing hormone release by activating the endocannabinoid system

“…Furthermore, ␤-endorphin inhibits nitric oxide synthase activity and naltrexone increases basal nitric oxide levels (10), indicating a tonic inhibitory ␤-endorphin action suppressing LHRH release by using the pathway described above.…”