Osmotic Inhibition of Neurohypophysial Secretion

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Abstract
Regulation of pituitary AVP and OT secretion is a complex process governed by both osmotic and nonosmotic afferent inputs to the neurohypophysis. Multiple lines of evidence indicate that nonosmotic afferent inputs consist of both excitatory and inhibitory units. Although excitatory osmotic afferent inputs have also been well described, this review summarizes data supporting the existence of sensitive and powerful inhibitory osmotic units as well. The simplistic view that volume regulatory influences on AVP secretion will always take precedence over osmoregulatory influences is clearly not in agreement with the accumulated data regarding osmotic inhibition of neurohypophysial secretion. A more appropriate model is one in which the net effect of these various excitatory and inhibitory influences on magnocellular secretory activity is determined by an integration of the activities of the various afferents, in concert with primary osmoreceptive properties of the magnocellular neurons themselves and other factors that act directly on magnocellular neurons (Fig. 1). The site(s) of action and the chemical nature of pathways subserving osmotic inhibition of neurohypophysial secretion remain to be ascertained. The most likely candidates at this time appear to be GABA projections from the ventral nucleus medianus to the SON and PVN, and endogenous opioid peptides acting either in the hypothalamus or directly at the neural lobe. This conceptual framework is consistent with the results of multiple studies of the interactive effects of osmotic and nonosmotic stimuli on neurohypophysial secretion that have demonstrated mutually interactive effects of these stimuli: volume status affects the threshold and gain of osmoregulated neurohypophysial secretion, and conversely osmotic status affects the magnitude of baroreceptor-mediated neurohypophysial secretion. When excitatory and inhibitory inputs are in conflict, the net effect on neurosecretion appears to be influenced not only by the respective magnitudes of the opposing stimuli, but also by the time course over which the stimuli develop. Consequently, although chronic hypoosmolality causes a potent inhibition of neurohypophysial secretion, acute nonosmotic stimuli of sufficient magnitude are still able to break through this inhibition. These results allow the possibility that clinical states of hypoosmolality due to inappropriate AVP secretion may be due either to the presence of excitatory nonosmotic stimuli that override osmotic inhibition, or alternatively to defects in the pathways or mechanisms underlying the osmotic inhibition itself.