title: Adrenalectomy abrogates reduction of 12-O-tetradecanoylphorbol-13-acetate-induced extracellular signal-regulated protein kinase activity in the epidermis of dietary energy-restricted SENCAR mice: implications of glucocorticoid hormone.
abstract: Previous studies in this laboratory demonstrated that dietary energy restriction (DER), a potent inhibitor of skin carcinogenesis, markedly suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced extracellular signal-regulated protein kinase (ERK) activity in mouse epidermis. Intact adrenal glands have been reported to be important in the inhibition of skin tumor promotion by food restriction. We investigated the role of adrenal glands and corticosterone in the DER effect on ERK activity. Female SENCAR mice, either sham operated or adrenalectomized (Adx), were prefed with 40% DER diet for 8-10 weeks and treated with a single TPA treatment or twice weekly TPA after initiation by 7,12-dimethylbenz(a)anthracene (DMBA). ERK activity measured 1 h after the last TPA treatment was significantly inhibited by DER in sham-operated mice, whereas the ERK inhibitory effect of DER was completely abolished in Adx mice. In a parallel study, Adx mice were provided with 60 microg/ml corticosterone in the drinking water to test the hypothesis that corticosterone from the adrenal gland plays a key role in the DER inhibition of ERK in mice with intact adrenal glands. There was an overall elevated plasma corticosterone level in DER mice compared with AL mice. Adx decreased the plasma corticosterone level and abrogated the DER inhibition of ERK activity. Addition of corticosterone in the drinking water restored plasma hormone level and markedly decreased TPA-induced ERK activity in Adx mice (P < 0.05). These results provide strong evidence that intact adrenal glands are essential for the DER inhibition of ERK induction by TPA and that corticosterone plays a critical role in the DER blockage of ERK induction.
authors.affiliation: Department of Food Science and Human Nutrition, Iowa State University, Ames, Iowa 50011, USA.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Liu
authors.forename: Weiqun
authors.initials: W
authors.lastname: Wang
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Hawley
authors.forename: Diane F
authors.initials: DF
authors.lastname: Birt
mesh_terms: D000315:Adrenalectomy / Q000009:adverse effects*; D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D018450:Disease Progression; D002149:Energy Intake; D004817:Epidermis / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D051379:Mice; D018632:Mice, Inbred SENCAR; D011494:Protein Kinases / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism*
chemical_list: D011494:Protein Kinases; D013755:Tetradecanoylphorbol Acetate; D003345:Corticosterone