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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Modified Research Career Development Award (K04)
Project #
5K04HD000968-04
Application #
2194437
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1992-04-01
Project End
1997-03-31
Budget Start
1995-04-01
Budget End
1996-03-31
Support Year
4
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Iowa
Department
Physiology
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Chen, S; Liu, X; Segaloff, D L (2000) A novel cyclic adenosine 3',5'-monophosphate-responsive element involved in the transcriptional regulation of the lutropin receptor gene in granulosa cells. Mol Endocrinol 14:1498-508
Chen, S; Shi, H; Liu, X et al. (1999) Multiple elements and protein factors coordinate the basal and cyclic adenosine 3',5'-monophosphate-induced transcription of the lutropin receptor gene in rat granulosa cells. Endocrinology 140:2100-9
Rozell, T G; Davis, D P; Chai, Y et al. (1998) Association of gonadotropin receptor precursors with the protein folding chaperone calnexin. Endocrinology 139:1588-93
Abell, A N; McCormick, D J; Segaloff, D L (1998) Certain activating mutations within helix 6 of the human luteinizing hormone receptor may be explained by alterations that allow transmembrane regions to activate Gs. Mol Endocrinol 12:1857-69
Davis, D P; Rozell, T G; Liu, X et al. (1997) The six N-linked carbohydrates of the lutropin/choriogonadotropin receptor are not absolutely required for correct folding, cell surface expression, hormone binding, or signal transduction. Mol Endocrinol 11:550-62
Jaquette, J; Segaloff, D L (1997) Temperature sensitivity of some mutants of the lutropin/choriogonadotropin receptor. Endocrinology 138:85-91
Abell, A N; Segaloff, D L (1997) Evidence for the direct involvement of transmembrane region 6 of the lutropin/choriogonadotropin receptor in activating Gs. J Biol Chem 272:14586-91
Thomas, D; Rozell, T G; Liu, X et al. (1996) Mutational analyses of the extracellular domain of the full-length lutropin/choriogonadotropin receptor suggest leucine-rich repeats 1-6 are involved in hormone binding. Mol Endocrinol 10:760-8
Abell, A; Liu, X; Segaloff, D L (1996) Deletions of portions of the extracellular loops of the lutropin/choriogonadotropin receptor decrease the binding affinity for ovine luteinizing hormone, but not human choriogonadotropin, by preventing the formation of mature cell surface receptor. J Biol Chem 271:4518-27
Rozzell, T G; Wang, H; Liu, X et al. (1995) Intracellular retention of mutant gonadotropin receptors results in loss of hormone binding activity of the follitropin receptor but not of the lutropin/choriogonadotropin receptor. Mol Endocrinol 9:1727-36

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