Gene regulation in the magnocellular hypothalamo-neurohypophysial system

The hypothalamo-neurohypophysial system (HNS) is the major peptidergic neur osecretory system through which the brain controls peripheral physiology. T he hormones vasopressin and oxytocin released from the HNS at the neurohypo physis serve homeostatic functions of water balance and reproduction. From a physiological viewpoint, the core question on the HNS has always been, "H ow is the rate of hormone production controlled?" Despite a clear descripti on of the physiology, anatomy, cell biology, and biochemistry of the HNS ga ined over the last 100 years, this question has remained largely unanswered . However, recently, significant progress has been made through studies of gene identity and gene expression in the magnocellular neurons (MCNs) that constitute the HNS. These are keys to mechanisms and events that exist in t he HNS. This review is an inventory of what we know about genes expressed i n the HNS, about the regulation of their expression in response to physiolo gical stimuli, and about their function. Genes relevant to the central ques tion include receptors and signal transduction components that receive and process the message that the organism is in demand of a neurohypophysial ho rmone. The key players in gene regulatory events, the transcription factors , deserve special attention. They do not only control rates of hormone prod uction at the level of the gene, but also determine the molecular make-up o f the cell essential for appropriate development and physiological function ing. Finally, the HNS neurons are equipped with a machinery to produce and secrete hormones in a regulated manner. With the availability of several ge ne transfer approaches applicable to the HNS, it is anticipated that new in sights will be obtained on how the HNS is able to respond to the physiologi cal demands for its hormones.