title: Time-dependent changes of levels of endogenous epidermal growth factor in submandibular glands, in kidneys, and in urine in rats during systemic treatment with EGF.
abstract: BACKGROUND
  Exogenous EGF influences the levels of endogenous EGF differently in the submandibular glands (SMG) and the kidneys. The aim of the present study was to examine the time-dependent changes in levels of endogenous EGF during 1-4 weeks of EGF treatment.
  
  
  METHODS
  Female rats were allocated into five groups receiving EGF subcutaneously (150 microg/kg/day) for 0 (controls), 1, 2, 3 and 4 weeks prior to sacrifice at an age of 12 weeks. At the end of the study period, 24-h urine samples were collected.
  
  
  RESULTS
  The weight of the SMG increased during EGF treatment (303+/-33 (controls), 359+/-37 (1 week EGF, P < 0.01), 390+/-30 (4 weeks EGF, P < 0.001) (mg mean+/-S.D.)). The EGF content of the SMG was unchanged after 1 week but threefold decreased after 4 weeks of treatment, respectively. The expression of EGF mRNA was decreased after 1 and 4 weeks as assessed with in situ hybridization. The weight of the kidneys was unchanged after 1 week and increased after 4 weeks of treatment (828+/-105 mg (controls) vs. 935+/-44 mg (4 weeks EGF, P < 0.005)). The renal content and the urinary excretion of EGF were significantly increased by 20-30% only in the group treated for 4 weeks.
  
  
  CONCLUSIONS
  EGF treatment induces a time-dependent decrease in the EGF content in the SMG most likely by reducing the biosynthesis of endogenous EGF. In contrast, the EGF content in kidneys and in urine was unchanged after 1 week and increased after prolonged treatment.
authors.affiliation: Department of Clinical Biochemistry, KH Aarhus University Hospital, Denmark. larsvj@dadlnet.dk
authors.forename: L
authors.initials: L
authors.lastname: Vinter-Jensen
authors.forename: P E
authors.initials: PE
authors.lastname: Jørgensen
authors.forename: J
authors.initials: J
authors.lastname: Thulesen
authors.forename: S S
authors.initials: SS
authors.lastname: Poulsen
authors.forename: E
authors.initials: E
authors.lastname: Nexø
mesh_terms: D000818:Animals; D004815:Epidermal Growth Factor / Q000494:pharmacology* / Q000652:urine; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013363:Submandibular Gland / Q000378:metabolism*; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D004815:Epidermal Growth Factor