The mechanism whereby steroid hormones control the release of hypothalamic releasing factors which in turn control the release of pituitary hormones is not well defined. We propose to examine the mechanism by which estrogen (E) inhibits the release of luteinizing hormone releasing factor (LRF) by the hypothalamus. Synaptosomes or nerve ending particles from the stalk median eminence (SME) region of the rat hypothalamus will be employed as a model to test the hypothesis that E acts in the hypothalamus to initiate the synthesis of a hypothalamic mediator protein (HMP) which in turn inhibits in dopamine (DA)-induced release of LRF. Synaptosomes of the SME will be prepared which are enriched for DA and LRF neuronal elements and which are capable of releasing LRF under electical, ionic, and DA stimulation. This synaptosomal preparation will allow us to examine potential modes of action of E (or HMP) and to correlate nuclear levels of receptor estrogen complex (R.E) with the inhibition of LRF release. Thus the metabolism, transport, storage, release, and postsynaptic binding of DA will be examined along with the electrical-, ionic-, and DA-induced release of LRF from SME synaptosomes. In addition, levels of nuclear R.E. will be correlated with alterations in these parameters. Just as the synaptosome has proven invaluable in the field of neurochemistry for studying the mechanism of synaptic transmission and the mode of drug action, so it offers the field of endocrinology a route for the elucidation of the mechanism whereby estrogens regulate LRF release.