ONTOGENY OF THE LUTINIZING HORMONE RELEASING HORMONE SYSTEM

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LHRH neurons are derived from the olfactory placode and migrate into the brain. The factors which dictate cell-specific LHRH gene expression and the migratory mechanism(s) used by the LHRH neurons during their movement into the CNS are currently unknown. Using immunocytochemistry and in situ hybridization histochemistry, we are examining the prenatal development of the LHRH system. We have found that an extracellular matrix molecule fibronectin, borders but does not enter the migratory pathway, whereas N-CAM, a cell adhesion molecule, is abundantly present within it. Hence, we propose the hypothesis that LHRH cells migrate to the brain using a positive (binding) interaction with N-CAM, and a negative interaction with fibronectin, and are testing this hypothesis using organotypic cultures of embryonic tissues. Transgenic mice in which the human LHRH promoter was fused to the SV 40 T-antigen have been generated, and these animals show abnormal reproductive function. No LHRH cells were found within the CNS but tumor masses in the nasal region were detected. From these tumors, a stable LHRH-positive cell line is being established.