title: Mechanism of androgen action: recent observations on the domain structure of androgen receptors and the induction of EGF-receptors by androgens in prostate tumor cells.
abstract: In this paper two different aspects of androgen action are reviewed. Polyacrylamide gel electrophoresis of androgen receptors, photoaffinity labeled with R1881 showed that receptors isolated from both human prostate cells and calf uterine cytosol cells are proteins with a molecular mass of approx 110 kD. Purification to homogeneity of this form of the receptor from calf uterus also yielded a 110 kD protein. A molecular model for the DNA-binding form of the receptor is presented in which one polypeptide comprises three active domains: one for ligand binding, one for interaction with nuclear acceptor sites, and a third domain which modulates nuclear interaction. Mild digestion with chymotrypsin or a protease from rat prostates removes the modulating domain and leaves the ligand binding and nuclear interaction domain intact. Trypsin treatment yields a fragment of lower molecular mass containing the ligand binding domain with some affinity for RNA, but not DNA. In vitro studies with a human prostate tumor cell line (LNCaP), suggest that androgens not only directly effect cell growth, but also act indirectly. Both epidermal growth factor (EGF) and androgens stimulate cell growth. In addition androgens stimulate synthesis of receptors for EGF. Thus androgens effect tumor cell growth by autocrine or paracrine mechanisms by making the cells more sensitive for growth factor mediated stimuli.
authors.affiliation: Department of Biochemistry (Division of Biochemical Endocrinology), Erasmus University Rotterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Mulder
authors.forename: D
authors.initials: D
authors.lastname: van Loon
authors.forename: W
authors.initials: W
authors.lastname: de Boer
authors.forename: A L
authors.initials: AL
authors.lastname: Schuurmans
authors.forename: J
authors.initials: J
authors.lastname: Bolt
authors.forename: M M
authors.initials: MM
authors.lastname: Voorhorst
authors.forename: G G
authors.initials: GG
authors.lastname: Kuiper
authors.forename: A O
authors.initials: AO
authors.lastname: Brinkmann
mesh_terms: D000728:Androgens / Q000502:physiology*; D000818:Animals; D002417:Cattle; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008297:Male; D011467:Prostate / Q000502:physiology; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D011944:Receptors, Androgen / Q000502:physiology*; D014599:Uterus / Q000502:physiology
chemical_list: D000728:Androgens; D011944:Receptors, Androgen; D066246:ErbB Receptors