HORMONAL REGULATION OF THE EGFlRECEPTOR SYSTEM

The EGFlreceptor system is involved in the development, maintenance and repair of various organs, particularly those involving ductal systems. Disruptions of the EGFlreceptor system have been implicated in a variety of clinical disorders including cancer and aging. Some hormones alter the expression of EGF ligands, EGF receptors and of downstream factors that mediate EGF receptor action during development. These hormonal effects vary according to the species, organ and stage of development under study. Androgens alter EGF mRNA levels in several rodent tissues, yet no androgen­ responsiveness is detectable within 7 kB upstream of the promoter of the EGF gene, which supports earlier evidence that androgens have post-transcriptional actions on EGF expression. A U-rich elements that can influence transcript stability and subcellular localization are present in the 3' UTR of EGF mRNA. Androgens regulate EGF mRNA polyadenylation site usage, poly-A tail length and mRNA stability in the mouse submaxillary salivary gland (SMG) but not in the kidney, although androgens do regulate other genes in the kidney. Androgens also regulate the levels of several A U-rich RNA binding proteins known to affect the subcellular localization, translation and stability of AU-rich mRNAs. Androgen-dependent changes in the subcellular levels of these RNA binding proteins also indicate a causal connection with the androgen-dependent changes in EGF mRNA and its translation.