NITRIC-OXIDE IS INVOLVED IN THE GENESIS OF PULSATILE LHRH SECRETION FROM IMMORTALIZED LHRH NEURONS

Neuronal networks controlling endocrine events present synchronous act ivity which is required for maintaining physiological functions, inclu ding reproduction, Although pulsatile hormone secretion is of paramoun t importance, the mechanism(s) by which secretory episodes are generat ed remain largely unknown, Nitric oxide (NO) has become the prototype of a new family of signaling molecules in the body. Nitric oxide diffu ses from the source cell and controls activity of neighboring neurons as well as itself as a retrograde messenger, Cells of the luteinizing hormone-releasing hormone (LHRH) neuronal network, the key component i n the control of reproduction, are scattered and loosely arranged in t he anterior hypothalamus. A diffusible neurotransmitter could provide a means for establishing synchronous activation of the LHRH neuronal n etwork leading to physiologically-relevant pulsatile LHRH secretion. I n this study, we demonstrate that immortalized LHRH-producing neurons (GT1-7 cells) express NO synthase (NOS) mRNA and protein, Furthermore, GT1-7 cells are NADPH-diaphorase-positive (a marker of NOS activity) and the histochemical reaction can be abolished by treatment with a co mpetitive NOS blocker, The presence of citrulline in these cells provi des further evidence for the biological activity of NOS, These observa tions indicate that an active NO synthesizing machinery is present in immortalized LHRH neurons, In addition, we show that LHRH secretion is enhanced by NO in a cGMP-dependent manner, Since pulsatile LHRH secre tion from immortalized LHRH neurons in vitro is abolished by NOS block ers and NO scavengers, it appears that NO is a unique neurotransmitter that is necessary to set LHRH neurons in phase to establish synchroni zed pulsatile LHRH secretion.