Androgens play an essential role in the differentiation, development and maintenance of epididymal function. However, the molecular mechanisms by which androgens regulate these processes are not completely understood. This laboratory has previously isolated and characterized an androgen dependent secretory protein of the rat epididymis, acidic epididymal glycoprotein (AEG). Using an affinity purified antibody to AEG, a cDNA clone for this protein has been isolated from a rat epididymal cDNA expression library.
Our aim i s to use this cDNA probe as a tool to study the effects of androgen on gene expression during epididymal development. The cDNA for AEG will be cloned and sequenced; regulatory sequences for translation will be identified. Studies will be initiated to investigate the in vivo effects of androgens on gene transcription by using the cDNA to detrmine mRNA levels and rates of synthesis during epididymal development. The cDNA will be used to isolate and characterize the gene for AEG; exons, introns, transcription start site and possible regulatory sequences will be mapped. Comparison of nucleotide sequence to that of the gene for prostatein, an androgen dependent protein of the rat ventral prostate, may lead to the identification of consensus sequences and possible androgen receptor binding sites. Mapping of DNAase I hypersensitive sites in the AEG gene before and after androgen withdrawal may lead to the identification of important regulatory sequences. The role of neonatal androgens on chromatin structure and gene expression will be determined by studying the effect of neonatal castration on DNAase I hypersensitive sites and mRNA levels. Long term goals include the development of an in vitro model to study the effect of androgens on epididymal cell function and the investigation of androgen regulation of epididymal differentiation in utero.
| Charest, N J; Zhou, Z X; Lubahn, D B et al. (1991) A frameshift mutation destabilizes androgen receptor messenger RNA in the Tfm mouse. Mol Endocrinol 5:573-81 |
| Charest, N J; Petrusz, P; Ordronneau, P et al. (1989) Developmental expression of an androgen-regulated epididymal protein. Endocrinology 125:942-7 |
| Charest, N J; Joseph, D R; Wilson, E M et al. (1988) Molecular cloning of complementary deoxyribonucleic acid for an androgen-regulated epididymal protein: sequence homology with metalloproteins. Mol Endocrinol 2:999-1004 |
