GONADOTROPIN RECEPTORS

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My career goals have been to attain a tenured position in an environment that will foster the growth of my research program. It is clear that the Department of Physiology and Biophysics at The University of Iowa offers such an environment. My research has focused upon the LH/CG and FSH receptors, whose functions play a pivotal role in reproductive physiology. We hope to learn in progressively greater detail the structure of these receptors and the mechanisms underlying their mechanism of action and regulation. These studies have been greatly advanced by our recent ability to clone the cDNA's for the rat LH/CG and FSH receptors. Thus, we now have the experimental tools to address important physiological questions concerning the biology of these receptors. Specifically, the overall specific aims that I have set for my laboratory for the next five years are to (1) examine the induction and/or regulation of ovarian and testicular LH/CG and FSH receptors at the levels of transcription and translation; (2) clone, express, and characterize the 5' flanking regions of the LH/CG and FSH receptor genes in order to study the cell-specific and hormonally-regulated expression of these receptors; and (3) map functional domains of the LH/CG and FSH receptors by constructing and characterizing mutant and chimeric forms of the receptors. The information gained from these studies will significantly aid in our understanding of the regulation of testicular and ovarian function, as well as human fertility and infertility. They will also contribute to our understanding of the mechanisms by which G protein-coupled receptors transmit extracellular events into intracellular signals. Salary support is being requested in order to reduce the amount of time I am obligated to spend in teaching and committee functions, allowing me to devote more of my time (at least 80%) to the laboratory. This will be critical for sustaining the momentum of my ongoing research, and thus further help establish myself as an independent investigator.