Hyponatremia in rats induces downregulation of vasopressin synthesis.

Hyponatremia due to inappropriate secretion of vasopressin is a common disorder in human pathophysiology, but vasopressin synthesis during hypoosmolality has not been investigated. We used a new method to quantitate synthesis of vasopressin in rats after 3, 7, and 14 d of hyponatremia induced by administering dDAVP (a vasopressin agonist) and a liquid diet. Vasopressin synthesis was completely turned off by 7 d. Vasopressin mRNA levels in the hypothalamus paralleled the reduction in synthesis and were reduced to levels of only 10-15% of the content in control rats. When hyponatremia was corrected by withdrawal of dDAVP, vasopressin mRNA slowly returned to normal over 7 d. The observation that vasopressin synthesis can be so completely turned off leads to several conclusions: under normal physiological conditions the neurohypophysis is chronically upregulated; there must be an osmotic threshold for initiation of vasopressin synthesis (and release); the large store of hormone in the posterior pituitary is essential for vasopressin to be available during times of decreased synthesis; and, finally, some nonosmolar stimulus for synthesis must be present during clinical disorders when vasopressin is secreted (and synthesized) despite hypoosmolality.

Total translation of vasopressin and oxytocin in neurohypophysis of rats.

There is a paucity of information about total translation rate of vasopressin and oxytocin. Because the site of synthesis of the neurohypophysial hormones is anatomically separate from the site of storage, we were able to measure total translation by blocking transport of newly synthesized hormone and measuring accumulation in the areas of synthesis in the hypothalamus. Colchicine administered into the third ventricle in doses as low as 3.5 micrograms/rat blocked transport for 18 h. The linear increase in vasopressin and oxytocin content over 18 h indicated a stable rate of synthesis, which was 1.2 and 1.9 pmol/h for vasopressin and 1.4-2.5 pmol/h for oxytocin. The molar correlation for synthesis of total neurophysin to total hormone was 1.16. Infusion of oxytocin and vasopressin into rats indicated that this level of synthesis of hormone was essential under steady-state conditions to maintain plasma levels in the low physiological range of approximately 3 pg/ml for oxytocin and 1 pg/ml for vasopressin. The data on total synthesis of the neurohypophysial hormones provide a reference for studies in which physiological replacement is required and also provide the technique and base-line data to determine how translation of vasopressin and oxytocin is regulated when neurohypophysial function is altered.