Hormones, Brain Plasticity and Reproductive Functions

Abstract

The magnocellular oxytocin system of the hypothalamus illustrates remarkably well activity-dependent structural plasticity in the adult brain. Its neurons secrete the neurohormone oxytocin, which plays a key role in the initiation of parturition and maintenance of lactation. The somata and dendrites of oxytocin neurons accumulate in the supraoptic and paraventricular nuclei of the hypothalamus whereas their axons project to the neurohypophysis. There, oxytocin is secreted into the bloodstream from neurosecretory terminals upon electrical and biosynthetic activation of the neurons driven by afferent stimulation from the periphery. Oxytocin is released centrally as well, including within the hypothalamic nuclei, where it facilitates the electrical, biosynthetic and secretory activities of its own neurons. During conditions that stimulate peripheral and central oxytocin release, like parturition and lactation, there is a significant reduction in ensheathing of oxytocin neurons and their synapses by fine processes of astrocytes. As a consequence, the geometry and diffusion properties of the extracellular space surrounding the cells are significantly modified. In addition, there is a concomitant formation of new functional synapses on oxytocin neurons, which, in the main, are inhibitory. The anatomical changes are rapid, occuring within an hour, and reversible with arrest of stimulation. In vivo and in vitro evidence shows that oxytocin, in synergy with estrogen, mediates this neuronal, glial and synaptic remodeling. It is mediated specifically by oxytocin receptors, requires de novo protein synthesis, ongoing neuronal activity and expression of cell adhesion molecules that are permissive for plasticity. Similar neuro-glial changes occur in other hypothalamic nuclei whose neurons intervene in estrogen-dependent reproductive behaviors, like ovarian cyclicity and puberty. The functional consequences of such structural plasticity are important since the plasticity modifies neurotransmission, gliotransmission, neurohormone secretion and, ultimately, behaviors associated with reproduction.