The function of the Gonadotropin Releasing Hormone (GnRH) gene is central to the reproductive capability of mammalian organisms. At the cellular level many factors may act to regulate the production of the GnRH decapeptide via effects on transcription, translation and post-translational events. The structures of the mRNA and genomic locus encoding the GnRH precursor in the rat and human have been described. Further work revealed that the DNA in the rat which encodes the GnRH precursor on one DNA strand, also encodes a distinct gene, SH, on the opposite DNA strand. The SH and GnRH genes share significance exonic sequences and the RNAs transcribed from either strand show distinct but overlapping patterns of tissue and cellular specificity. The major goal of the research proposed here is to more thoroughly characterize the GnRH:SH gene locus and examine the functional relationship between the GnRH and SH gene products. First, will be to localize the promoter elements present on both strands of the GnRH:SH gene by mapping transcriptional initiation sites, and by assaying the ability of implicated genomic sequences to drive expression of reporter genes. Second, will be to determine if the SH RNAs produce proteins in vivo. Third, will be to determine whether there are cells which co-express the GnRH and SH genes. Fourth, will be to examine the consequences of expressing the GnRH and SH genes within the same cells. By studying the structure and function of the GnRH:SH gene locus in this way, we hope to answer questions regarding the regulation of the reproductive control molecule GnRH, the function of the SH gene, and the significance of this novel eukaryotic genetic arrangement.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD024562-01
Application #
3325252
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1988-12-01
Project End
1991-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Overall Medical
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
Valdes, C T; Elkind-Hirsch, K E; Rogers, D G et al. (1991) The hypothalamic-pituitary axis of streptozotocin-induced diabetic female rats is not normalized by estradiol replacement. Endocrinology 128:433-40
Cook, P W; Mattox, P A; Keeble, W W et al. (1991) A heparin sulfate-regulated human keratinocyte autocrine factor is similar or identical to amphiregulin. Mol Cell Biol 11:2547-57
Kavanaugh, M P; Christie, M J; Osborne, P B et al. (1991) Transmitter regulation of voltage-dependent K+ channels expressed in Xenopus oocytes. Biochem J 277 ( Pt 3):899-902
Douglass, J O; Christie, M; Adelman, J P et al. (1991) Characterization of mammalian potassium channel genes. NIDA Res Monogr 111:54-68
Busch, A E; Hurst, R S; North, R A et al. (1991) Current inactivation involves a histidine residue in the pore of the rat lymphocyte potassium channel RGK5. Biochem Biophys Res Commun 179:1384-90
Bond, C T; Francis, R C; Fernald, R D et al. (1991) Characterization of complementary DNA encoding the precursor for gonadotropin-releasing hormone and its associated peptide from a teleost fish. Mol Endocrinol 5:931-7
Daikh, D I; Douglass, J O; Adelman, J P (1989) Structure and expression of the human motilin gene. DNA 8:615-21
Bond, C T; Hayflick, J S; Seeburg, P H et al. (1989) The rat gonadotropin-releasing hormone: SH locus: structure and hypothalamic expression. Mol Endocrinol 3:1257-62