The proposal will attempt to determine whether the induction of new connections between neurons in the hypothalamus produced by the administration of estradiol, is dependent on the synthesis of prostaglandins. The ability to induce an LH surge under these conditions will be tested as well as the content of Prostaglandin E2 in the hypothalamus. This proposal will also attempt to isolate and measure the protein(s) that are altered during estrogen-induced synaptogenesis. The major hypothesis in that portion of the proposal is that estradiol stimulates the production of a structural protein(s) that makes up the new synapses. The proposal will attempt to determine whether the synaptogenic effect of estradiol is reflected by incorporation of precursor amino acids into new proteins, that will be isolated and measured using autofluorography. Finally, this proposal will attempt to identify steroid receptor molecules, using immunoblotting techniques, in an attempt to determine whether the new proteins increased by estrogen are binding ovarian steroids. This proposal will be a major attempt to determine a number of factors involved in the creation of new neuronal connections in prepuberal animals. The proposal will attempt to bridge areas in neurochemistry, molecular biology, neuroendocrinology, and ultrastructural analysis. The outcome of this proposal will be of extreme importance, not only to our understanding of the mechanisms controlling anterior pituitary gland hormone release, but also in the possible identification of a factor that is responsible for new synaptic growth in the central nervous system. The isolation and use of such a factor could be of great help on the treatment of neurodegenerative diseases as well as neurological trauma.
