We have previously shown that cells of the immune system can produce a host of neuroendocrine hormone-like peptides and also be acted upon by these same hormones. This has led to the concept that bidirectional communication between the immune and neuroendocrine systems occurs biochemically as a result of a shared set of hormones and their receptors. The ultimate proof of this theory seems to reside in a basic understanding of the primary structure of immunologically-derived hormones and their receptors as well as knowledge of their in vivo functions. This constitutes the overall objective of this research proposal, and this will be accomplished primarily through molecular biological techniques such as cDNA cloning, polymerase chain reactions and cDNA sequencing. Specifically, we intend to clone and sequence the cDNAs for leukocyte- derived pro-opiomelanocortin (POMC), thyrotropin (TSH), chorionic gonadotropin (CG), luteinizing hormone (LH) as well as the delta opiate and LH releasing hormone (RH) receptors. Comparison of these sequences with those of the neuroendocrine counterparts would constitute a definitive test of the aforementioned concept. The possible in vivo function as well as cellular source of immunologically-derived ACTH, TSH, and LH will be assessed in hypophysectomized mice. Specifically, we will determine whether such animals exhibit the appropriate hormonal response following corticotropin releasing factor (CRF), thyrotropin releasing hormone (TRH), and LHRH treatment, respectively. If so, we will attempt to ablate the response by immunodepletion techniques. Successful completion of these studies should yield pivotal information on a communication circuit between the immune and neuroendocrine systems. An understanding of this circuitry could lead to many new ideas for the detection, prophylaxis and therapy of human diseases.