PROTOONCOGENE C-FOS AND THE REGULATION OF VASOPRESSIN GENE-EXPRESSIONDURING DEHYDRATION

Secretion of the antidiuretic hormone (ADH) vasopressin is increased w hen body fluid homeostasis is disturbed by dehydration. Associated wit h this increased secretion is an elevation of vasopressin mRNA in magn ocellular hypothalamic neurons projecting to the posterior pituitary. The proto-oncogene c-fos codes for a nuclear phospho-protein Fos which binds to specific DNA elements and acts as a transcriptional regulato r coupling short-term extracellular stimuli to long-term responses by altering secondary target gene expression. This study in rats examined the time courses of dehydration induced c-fos expression and the chan ge of vasopressin gene expression in the magnocellular neurons of the hypothalamus. Immunocytochemical and in situ hybridization study demon strated that c-fos was induced by acute intracellular dehydration in t he hypothalamic magnocellular nuclei of paraventricular (PVN), supraop tic (SON), and accessory groups such as nucleus circularis. Double-lab el immunocytochemical study co-localized Fos and vasopressin-neurophys in immunoreactivity in the same magnocellular neurons in the SON and P VN. In situ hybridization analysis after acute dehydration revealed a rapid and transient c-fos induction followed by a persistent increase in vasopressin mRNA for up to 2 days even after rehydration. Furthermo re, prevention of c-fos translation by pretreatment with protein synth esis inhibitor cycloheximide attenuated this dehydration induced incre ase in vasopressin mRNA. This study demonstrated that an increase in v asopressin transcription after acute dehydration is dependent on an ea rly phase of protein synthesis.