MODULATING MECHANISMS OF NEUROENDOCRINE CELL-ACTIVITY - THE LHRH PULSE-GENERATOR

1. Luteinizing hormone-releasing hormone (LHRH), synthesized in specia lized neurons in the hypothalamus, is the prime regulator of reproduct ion. In its absence, reproductive development is arrested and disorder s of LHRH secretion result in several reproductive dysfunctions, 2. Th e LHRH neuronal network plays a paramount role in the regulatory loop controlling gonadal homeostasis. LHRH input to the pituitary gland mai ntains gonadotropin secretion, which, in turn, is responsible for gona dal trophism, Steroidal and peptidergic hormones from the gonad close the regulatory system by establishing negative (male and females) and positive (females) feedback loops. 3. Interestingly, LHRH input to the pituitary is intermittent rather than continuous. In fact, continuous exposure to LHRH results in paradoxical hypogonadism, Several studies in animals have provided direct evidence for episodic secretion of LH RH into the hypophyseal portal system. However, the nature of the syst em(s) responsible for the generation of the LHRH pulsatile profile is not currently known. The recent observation that immortalized LHRH neu rons secrete LHRH in a pulsatile manner suggests that the pulse genera ting mechanism resides within the LHRH neuronal network, 4. In this ov erview, we compile several lines of evidence supporting this notion an d put this characteristic of LHRH neurons in perspective with gonadal influences both internal and external to the LHRH neuronal network. So me recent data regarding the site of action of gonadal steroids on the LHRH neuronal system, the functional significance of Salanin colocali zation with LHRH, and the role of nitric oxide in the pulse generating mechanism are also discussed.