INTERACTION BETWEEN NO AND OXYTOCIN - INFLUENCE ON LHRH RELEASE

Nitric oxide synthase (NOS)-containing neurons have been localized in various parts of the CNS, These neurons occur in the hypothalamus, mos tly in the paraventricular and supraoptic nuclei and their axons proje ct to the neural lobe of the pituitary gland. We have found that nitri c oxide (NO) controls luteinizing hormone-releasing hormone (LHRH) rel ease from the hypothalamus acting as a signal transducer in norepineph rine (NE)-induced LHRH release, LHRH not only releases LH from the pit uitary but also induces sexual behavior. On the other hand, it is know n that oxytocin also stimulates mating behavior and there is some evid ence that oxytocin can increase NE release, Therefore, it occurred to us that oxytocin may also stimulate LHRH release via NE and NO. To tes t this hypothesis, we incubated medial basal hypothalamic (MBH) explan ts from adult male rats in vitro. Following a preincubation period of 30 min, MBH fragments were incubated in Krebs-Ringer bicarbonate buffe r in the presence of various concentrations of oxytocin, Oxytocin rele ased LHRH at concentrations ranging from 0.1 nM to 1 mu M with a maxim al stimulatory effect (P<0.001) at 0.1 mu M, but with no stimulatory e ffect at 10 mu M. That these effects were mediated by NO was shown by the fact that incubation of the tissues with N-G-monomethyl-L-arginine (NMMA), a competitive inhibitor of NOS, blocked the stimulatory effec ts. Furthermore, the release of LHRH by oxytocin was also blocked by p razocin, an alpha(1)-adrenergic receptor antagonist, indicating that N E mediated this effect. Oxytocin at the same concentrations also incre ased the activity of NOS (P<0.01) as measured by the conversion of [C- 14]arginine to citrulline, which is produced in equimolar amounts with NO by the action of NOS, The release of LHRH induced by oxytocin was also accompanied by a significant (P<0.02) increase in the release of prostaglandin E(2) (PGE(2)), a mediator of LHRH release that is releas ed by NO. On the other hand, incubation of neural lobes with various c oncentrations of sodium nitroprusside (NP) (300 or 600 mu M), a releas er of NO, revealed that NO acts to suppress (P<0.01) the release of ox ytocin. Therefore, our results indicate that oxytocin releases LHRH by stimulating NOS via NE, resulting in an increased release of NO, whic h increases PGE(2) release that in turn induces LHRH release, Furtherm ore, the released NO can act back on oxytocinergic terminals to suppre ss the release of oxytocin in an ultrashort-loop negative feedback.