In situ hybridization histochemistry and immunocytochemistry were used to study the prenatal expression of luteinizing hormone-releasing hormone (LHRH) cells in the mouse. Cells expressing LHRH mRNA and peptide product were first detected on embryonic day 11.5 (E11.5) in the olfactory pit. On E12.5, the majority of LURH cells were located on "tracks" extending from the olfactory pit to the base of the telencephalon. From E12.5 to E15. toradiography was used to determine when LHRH cells left the mitotic cycle. We show that LHRH neurons exhibit a discrete time of birth, suggesting that they arise as a single neuronal population between E10.0 and E11.0. Postnatal LHRH neurons were "birth-dated" shortly after differentiation of the olfactory placode and before LHRH mRNA was expressed in cells in the olfactory pit. Taken together, these studies support the hypothesis that all LHRH cells in the central nervous system arise from a discrete group of progenitor cells in the olfactory placode and that a subpopulation of these cells migrate into forebrain areas where they subsequently establish an adult-like distribution.It has been proposed (1, 2) that luteinizing hormone-releasing hormone (LHRH) neurons in the mouse originate in the olfactory placode and migrate into forebrain areas during prenatal development. Prior to this hypothesis, it had been assumed that forebrain LHRH cells had multiple embryonic origins, since the anatomical distribution of forebrain LHRH cells in postnatal animals spanned neuronal areas that normally develop from different regions of the neuroepithelium (3). The "olfactory placode" hypothesis for the ontogeny of mouse forebrain LHRH neurons was largely based on the observations that immunopositive cells were first detected in the olfactory pit and that the spatiotemporal distribution of LHRH cells progressed from nasal regions into the forebrain during embryonic development (1, 2). The latter studies used antibodies directed against LHRH (1, 2) and the gonadotropin-releasing hormone-associated peptide (1).In this study, we use in situ hybridization histochemistry for LHRH mRNA as well as immunocytochemistry for the LHRH peptide to study the prenatal expression of the LHRH gene in cells in the embryonic mouse. The use of oligonucleotide probes for mRNA eliminates misidentification by possible antibody crossreactivity with non-LHRH epitopes. In addition, by using in situ hybridization histochemistry, it is possible to determine if embryonic forebrain areas, which are known to contain LHRH cells postnatally, have LHRH mRNA-containing cells that are LHRH peptide deficient. If such cells exist, it would suggest that forebrain LHRH cells, which may be delayed in peptide synthesis or processing, could originate in the brain itself. Alternatively, if cells expressing LHRH mRNA show the same onset and spatiotemporal distribution as previously reported for immunopositive cells (1, 2), then the hypothesis (1, 2, 4) that all LHRH cells found in the brain originate in the olfactory placode would be ...

Vasopressin and oxytocin are made and released by neurons of the hypothalamo-neurohypophysial system. Pulse labeling these neurons with radioactive amino acid indicates that the two hormones and their respective neurophysin carrier proteins are synthesized as parts of separate precursor proteins. The precursors seem to be processed into smaller, biologically active molecules while they are being transported along the axon.

The hypothalamo-neurohypophysial system (HNS) is the major peptidergic neurosecretory system through which the brain controls peripheral physiology. The hormones vasopressin and oxytocin released from the HNS at the neurohypophysis serve homeostatic functions of water balance and reproduction. From a physiological viewpoint, the core question on the HNS has always been, "How is the rate of hormone production controlled?" Despite a clear description of the physiology, anatomy, cell biology, and biochemistry of the HNS gained 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 the HNS. This review is an inventory of what we know about genes expressed in the HNS, about the regulation of their expression in response to physiological stimuli, and about their function. Genes relevant to the central question include receptors and signal transduction components that receive and process the message that the organism is in demand of a neurohypophysial hormone. The key players in gene regulatory events, the transcription factors, deserve special attention. They do not only control rates of hormone production at the level of the gene, but also determine the molecular make-up of the cell essential for appropriate development and physiological functioning. Finally, the HNS neurons are equipped with a machinery to produce and secrete hormones in a regulated manner. With the availability of several gene transfer approaches applicable to the HNS, it is anticipated that new insights will be obtained on how the HNS is able to respond to the physiological demands for its hormones.