title: The mitogenic effect of testosterone and 17β-estradiol on airway smooth muscle cells.
abstract: Airway disease distribution and/or severity exhibit sex differences suggesting that sex hormones are involved in the respiratory system physiology and pathophysiology. The implication of airway smooth muscle cells (ASMCs) in the physiology of the airways and the pathogenetic mechanism of airway remodeling is of great interest. Therefore, we studied the effect of testosterone and 17β-estradiol on ASMC proliferation and the mechanisms involved. Cell proliferation was estimated using the methyl-[³H]thymidine incorporation and Cell Titer 96® AQueous One Solution Assay methods. ASMC isolated from adult male or female rabbit trachea were incubated with testosterone (1 pM-1 μM) or 17β-estradiol (1 pM-1 μM), in the presence or absence of the androgen receptor antagonist flutamide (10 nM) or estrogen receptor antagonist ICI182780 (10 nM), as well as of the PI3K inhibitors LY294002 (20 μM) or wortmannin (1 μM), or the MAPK inhibitors PD98059 (100 μM) or U0126 (1 μM). After 24 h of incubation, testosterone and 17β-estradiol increased methyl-[³H]thymidine incorporation and cell number, in ASMC isolated from male or female animals. The induction of ASMC proliferation by testosterone or 17β-estradiol was inhibited by flutamide or ICI182780 respectively, as well as by LY294002, wortmannin, PD98059 or U0126. In conclusion, testosterone and 17β-estradiol have a mitogenic effect on ASMC, which is receptor-mediated and involves the MAPK and PI3K signaling pathways. Moreover, their effect is the same for ASMC from male and female animals. It is possible that gender-related differences in ASMC remodeling, may be influenced by the different patterns of sex steroid hormone secretion in males and females.
authors.affiliation: Department of Physiology, Medical School, University of Thessaly, Greece.
authors.forename: Rodopi
authors.initials: R
authors.lastname: Stamatiou
authors.forename: Efrosyni
authors.initials: E
authors.lastname: Paraskeva
authors.forename: Maria
authors.initials: M
authors.lastname: Papagianni
authors.forename: Paschalis Adam
authors.initials: PA
authors.lastname: Molyvdas
authors.forename: Apostolia
authors.initials: A
authors.lastname: Hatziefthimiou
mesh_terms: D059002:Androgen Receptor Antagonists / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008934:Mitogens / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects*; D009570:Nitriles / Q000494:pharmacology; D011817:Rabbits; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors; D013739:Testosterone / Q000494:pharmacology*; D014132:Trachea / Q000166:cytology*; D000077191:Wortmannin
chemical_list: D059002:Androgen Receptor Antagonists; D000730:Androstadienes; D002070:Butadienes; D002867:Chromones; D047908:Intracellular Signaling Peptides and Proteins; D008934:Mitogens; D009025:Morpholines; D009570:Nitriles; D011960:Receptors, Estrogen; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D013739:Testosterone; D004958:Estradiol; D005485:Flutamide; D000077191:Wortmannin