Proenkephalin gene regulation in the neuroendocrine hypothalamus: a model of gene regulation in the CNS.

During the past decade, a great deal of progress has been made in studying the mechanisms by which transcription of neuropeptides is regulated by second messengers and neural activity. Such investigations, which have depended to a great extent on the use of transformed cell lines, are far from complete. Yet a major challenge for the coming decade is to understand the regulation of neuropeptide genes by physiologically and pharmacologically relevant stimuli in appropriate cell types in vivo. The proenkephalin gene, a member of the opioid gene family, has served as a model to study regulated transcription, not only in cell lines, but also in central (e.g., hypothalamic) and peripheral (e.g., adrenal) neuroendocrine tissues. Here we review regulation of proenkephalin gene expression in the hypothalamus. Several approaches, including in situ hybridization, use of transgenic mice, and the adaptation of electrophoretic mobility shift assays to complex tissues, have played critical roles in recent advances. A summary of possible future developments in this field of research is also presented.