Models of neurohypophyseal homeostasis

Rats subject to prolonged (3-6 days) hypernatremia show significantly decreased pituitary vasopressin content as well as increased levels of hypothalamic vasopressin mRNA; these values return to baseline levels after the stimulus is removed. In this paper, we tested whether a single cellular mechanism for regulation of synthesis could account for the experimental observations of both pituitary hormone depletion-repletion and hypothalamic mRNA content. We developed several "minimal" models of vasopressin synthesis in which control of hormone synthesis was regulated exclusively by transcription, translation, or mRNA decay and tested each model to see which best emulated the dynamics of neuro-hypophyseal vasopressin content and hypothalamic vasopressin mRNA. Experimental data provided parameters for pituitary content, baseline and stimulated release rates, mRNA decay, transcription, and translation. Models based exclusively on translation and mRNA decay failed to produce predictions similar to experimental observations. Of the models tested, the transcription model provided predictions most consistent with laboratory data, although some quantitative differences remain. The results of the computer modeling strongly suggest that transcription represents the predominant means by which magnocellular neurons regulate vasopressin synthesis.