Modulating mechanisms of neuroendocrine cell activity: the LHRH pulse generator.

1. Luteinizing hormone-releasing hormone (LHRH), synthesized in specialized neurons in the hypothalamus, is the prime regulator of reproduction. In its absence, reproductive development is arrested and disorders of LHRH secretion result in several reproductive dysfunctions. 2. The LHRH neuronal network plays a paramount role in the regulatory loop controlling gonadal homeostasis. LHRH input to the pituitary gland maintains gonadotropin secretion, which, in turn, is responsible for gonadal 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 LHRH into the hypophyseal portal system. However, the nature of the system(s) responsible for the generation of the LHRH pulsatile profile is not currently known. The recent observation that immortalized LHRH neurons secrete LHRH in a pulsatile manner suggests that the pulse generating mechanism resides within the LHRH neuronal network. 4. In this overview, we compile several lines of evidence supporting this notion and put this characteristic of LHRH neurons in perspective with gonadal influences both internal and external to the LHRH neuronal network. Some recent data regarding the site of action of gonadal steroids on the LHRH neuronal system, the functional significance of galanin colocalization with LHRH, and the role of nitric oxide in the pulse generating mechanism are also discussed.