The juvenile hormone (JH) of insects maintains individuals in an immature stage, and in adults it induces deposition of yolk proteins (YP) in oocytes (vitellogenesis). That yolk formation is not only hormonally controlled, but is also under genetic regulation is evident from the many Drosophila melanogaster female sterile mutants which fail to produce yolky eggs. The objective of the proposed research is to elucidate the interactions of genetic regulation and endocrine control governing specific protein synthesis in a eukaryote. The system is ideal to pursue this objective since it possesses (1) genetic manipulability; (2) a chemically defined inducer (JH); and (3) biochemically workable amounts of protein. The research will proceed in the following phases: (1) Specific YP's and enzymes will be identified electrophoretically which are absent in immature ovaries but are present in eggs and mature ovaries. Genetic (electrophoretic) variants of these proteins will be sought and genetically characterized. (2) The tissue of synthesis will be ascertained for each YP and egg enzyme. The molecular mechanism of JH induction will be studied employing in vitro tissue culture and using radiolabeled protein and nucleic acid precursors and metabolic inhibitors. (3) Two types of control mutants will be searched for: (a) mutants able to produce YP even in the absence of the inducer, and (b) mutants closely linked to the YP locus which alter inducibility of YP. (4) Finally, the molecular and genetic interactions of the control mutant, the hormone inducer, and YP synthesis will be studied. The research has importance for human health on two levels: (1) Many human diseases, including cancer have a genetic basis or result from aberrant gene control. Yet no general model of gene regulation has been proven to hold for eukaryotes. This research provides the opportunity for understanding control of gene function in higher animals. (2) Many human diseases are transmitted by insect vectors, which can be controlled if we regulate insect reproduction. To put regulation of insect reproduction on a rational basis it is necessary to understand the causative factors in insect fertility. The proposed research directly addresses this problem.