Vasopressin transport regulation is coupled to the synthesis rate

Vasopressin is synthesized in the perikarya of magnocellular neurons and is transported down long axons to the storage terminals of the posterior pituitary. To maintain stable pituitary stores following vasopressin secretion, the hypothalamus must synthesize and transport an amount of new vasopressin, equivalent to the amount released. Vasopressin release and synthesis rate can be chronically upregulated or suppressed relative to basal levels, depending on the demand for vasopressin. We studied whether vasopressin transport was similarly regulated during situations of varying demand. During chronic hyponatremia, when synthesis of vasopressin was reduced to undetectable levels, transport of vasopressin was also markedly decreased, as evidenced by continued presence of vasopressin in the transport system. Upregulation of transport was demonstrated by measuring pituitary accumulation of vasopressin in rats whose pituitary stores were initially depleted by hypernatremia and in whom subsequent release was suppressed by hyponatremia. In hypernatremic rats, transport of vasopressin was increased fivefold over baseline as determined by pituitary accumulation, and this elevated rate persisted for 7 days in the absence of release. This study demonstrates that axonal transport of vasopressin is a regulated process and is linked to synthesis rate rather than release.