Surgical stress delays prostate involution in mice.
Androgens control growth of prostate epithelial cells and androgen deprivation induces apoptosis, leading to prostate involution. We investigated the effects of surgical stress on prostate involution induced by androgen ablation and determined the underlying mechanisms. Androgen ablation in mice was induced by surgical castration and administration of the anti-androgenic drugs bicalutamide and MDV3100. Surgical stress was induced by sham castration under isoflurane anesthesia. Surgical stress delayed apoptosis and prostate involution induced by anti-androgenic drugs. These effects of stress were prevented by administering the selective beta2-adrenoreceptor antagonist ICI118,551 and were also blocked in BAD(3SA/WT) mice expressing phosphorylation-deficient mutant BAD3SA. These results indicate that apoptosis and prostate involution in response to androgen ablation therapy could be delayed by surgical stress via the beta2-adrenoreceptor/BAD signaling pathway. Thus, surgery could interfere with androgen ablation therapy, whereas administration of beta2-adrenoreceptor antagonists may enhance its efficacy.
Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
Sazzad
S
Hassan
Yelena
Y
Karpova
Anabel
A
Flores
Ralph
R
D'Agostino
George
G
Kulik
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000378:metabolism*; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D009154:Mutation; D009570:Nitriles / Q000494:pharmacology; D009919:Orchiectomy; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological; D014105:Tosyl Compounds / Q000494:pharmacology; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D000726:Androgen Antagonists; D000728:Androgens; D000813:Anilides; C494820:Bad protein, mouse; D001549:Benzamides; D009570:Nitriles; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; D014105:Tosyl Compounds; D051025:bcl-Associated Death Protein; D010669:Phenylthiohydantoin; C026777:ICI 118551; C540278:enzalutamide; C053541:bicalutamide