Interaction between NO and oxytocin: influence on LHRH release

Area of Science:

• Neuroendocrinology
• Neurophysiology

Background:

• Nitric oxide synthase (NOS)-containing neurons are present in the hypothalamus, influencing hormone release.
• Norepinephrine (NE) and nitric oxide (NO) are implicated in regulating luteinizing hormone-releasing hormone (LHRH) release.
• Oxytocin is known to stimulate mating behavior and may influence NE release.

Purpose of the Study:

• To investigate the role of oxytocin in stimulating LHRH release.
• To determine if NE and NO mediate oxytocin-induced LHRH release.
• To explore the feedback mechanism of NO on oxytocin release.

Main Methods:

• Incubation of medial basal hypothalamic (MBH) explants from male rats in vitro.
• Measurement of LHRH release in response to varying oxytocin concentrations.
• Assessment of nitric oxide synthase (NOS) activity using [14C]arginine conversion.
• Inhibition studies using NG-monomethyl-L-arginine (NMMA) and prazocin.
• Measurement of prostaglandin E2 (PGE2) release.
• Incubation of neural lobes with sodium nitroprusside (NP) to assess oxytocin release.

Main Results:

• Oxytocin stimulated LHRH release in a dose-dependent manner (0.1 nM to 1 microM), with maximal effect at 0.1 microM.
• The stimulatory effect of oxytocin on LHRH release was blocked by NMMA and prazocin, indicating mediation by NO and NE.
• Oxytocin increased NOS activity and PGE2 release.
• NO suppressed oxytocin release from neural lobes.

Conclusions:

• Oxytocin stimulates LHRH release via NE, leading to increased NO production, which in turn enhances PGE2 release and subsequently LHRH release.
• Released NO acts on oxytocinergic terminals to suppress oxytocin release, establishing an ultrashort-loop negative feedback.
• These findings elucidate a novel neuroendocrine pathway involving oxytocin, NE, NO, and PGE2 in the regulation of LHRH and oxytocin secretion.