Neuropeptide oxytocin facilitates its own brain-to-periphery uptake

The hypothalamo-neurohypophyseal system is a neuroendocrine conduit through which the neurohormones oxytocin and arginine vasopressin are released from the brain into the general circulation, influencing functions like salt balance and reproduction. However, the precise mechanism for rapid neurohormone transport to the periphery remains unclear. We show, using live imaging in zebrafish, that both hyperosmotic physiological challenge and optogenetic stimulation of oxytocin neurons elicit a local increase in neurohypophyseal blood flow velocities and a change in capillary diameter. This response is dictated by the geometry of the hypophyseal vascular microcircuit. Genetic ablation of oxytocin neurons and inhibition of oxytocin receptor signaling attenuate the changes in capillary blood flow and diameter. Both the osmotic challenge and oxytocin neuronal activation elicit a local rise in neurohypophyseal capillary permeability in an oxytocin-signaling-dependent manner. We propose that oxytocin-dependent neurovascular coupling facilitates its efficient uptake into the blood circulation, suggesting a self-perpetuating stimulus-secretion-uptake mechanism for peripheral hormone transfer.