title: Androgen action in the epididymis.
abstract: Androgens are responsible for maintaining epididymal structure and  functions. However, little is known about how androgen action is mediated and  the mechanisms underlying the restoration of the integrity of epididymal cells  after androgen deprivation. We first provide an overview of what is known  about androgen action in this tissue and then present data on the initial and  sequential roles of androgens in altering cellular architecture and function  in an androgen-deprived condition. Using morphometric analysis and the rat  model, we identified changes in epithelial cell height and lumen diameter, as  well as in the numbers of proliferating cells in different regions and at  various time points after androgen withdrawal and replacement. The sequence of  gene activation or suppression that occurred in the androgen-deprived tissue  was examined upon the readministration of the 2 active metabolites of  testosterone, dihydrotestosterone (DHT) and estradiol. Although few genes were  regulated by estradiol, many were affected by DHT. Epidermal growth factor  (EGF) and insulinlike growth factor-1 (IGF1) appear to play an important role  in the early response pathway activated by DHT because of their function in  the regulation of the expression of many other genes. The intracellular  signaling pathway involved in mediating the action of androgen in restoring  epididymal epithelial cell integrity was investigated using the PC-1  epididymal cell line. IGF1 and EGF receptors were found to be important  mediators of androgen receptor-mediated activation of the MAPK/ERK  pathways. Together, these studies provide a greater understanding of the  mechanisms of androgen action in the epididymis.
authors.affiliation: Department of Pharmacology & Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada. bernard.robaire@mcgill.ca
authors.forename: Bernard
authors.initials: B
authors.lastname: Robaire
authors.forename: Mahsa
authors.initials: M
authors.lastname: Hamzeh
mesh_terms: D000728:Androgens / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000378:metabolism; D004822:Epididymis / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism
chemical_list: D000728:Androgens; D011944:Receptors, Androgen; D004958:Estradiol; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1