ESTRADIOL AND PROGESTERONE REGULATE NEURONAL STRUCTURE AND SYNAPTIC CONNECTIVITY IN ADULT AS WELL AS DEVELOPING BRAIN

Until recently, it has been widely believed that the adult brain does not undergo changes in its structure, particularly in relation to the actions of circulating hormones. It has now become clear that estradio l and progesterone have important effects on adult brain structure and function. Single section Golgi silver staining and electron microscop y have been used to analyze numbers of spines on dendrites and to coun t synapses on dendritic spines. In the adult female rat brain, we find that dendrites of neurons in the ventromedial hypothalamus and CA1 re gion of the hippocampus sprout increased numbers of spines on dendrite s and then lose them during the 4- or 5-day estrous cycle. Increased s pine numbers are accompanied by increased numbers of synapses on spine s. In the hippocampus, the loss of spines and spine synapses occurs du ring a 24-h period between the time of maximum sexual receptivity on t he day of proestrus and the next day, the day of estrus. This loss is not due solely to the decline in estradiol; however, giving progestero ne speeds up the decline, and administering the antiprogestin, Ru486, on proestrus blocks the natural decline of synapse density. The change s of synaptic density in the hypothalamus are responsible, at least in part, for the cyclicity of sexual behavior, whereas the cyclicity of synapses in the hippocampus may subserve functions related to spatial learning and memory. In human subjects, cyclic fluctuations in gonadal hormones are associated with cyclic changes in performance on a varie ty of cognitive and motor tasks.