Tolloid-like 1 is negatively regulated by stress and glucocorticoids.
Glucocorticoids affect a variety of tissues to enable the organism to adapt to the stress. Hippocampal neurons contain glucocorticoid receptors and respond to elevated glucocorticoid levels by down-regulating the HPA axis. Chronically, however, stress is deleterious to hippocampal neurons. Chronically elevated levels of glucocorticoids result in a decrease in the number of dendritic spines, reduced axonal growth and synaptogenesis, and decreased neurogenesis in the hippocampus. Tolloid-like 1 (Tll-1) is a metalloprotease that potentiates the activity of the bone morphogenetic proteins (BMPs). Neurogenesis in the hippocampus of both developing and adult mammals requires BMPs. In this study, we demonstrate that Tll-1 expression is increased in mice that have increased neurogenesis. The Tll-1 promoter contains glucocorticoid response elements which are capable of binding to purified glucocorticoid receptor. Glucocorticoids decrease Tll-1 expression in vitro. Finally, prenatal stress leads to a decrease in Tll-1 mRNA expression in the hippocampus of adult female mice that is not observed in adult male mice indicating that Tll-1 expression is differentially regulated in males and females. The results of this study indicate that Tll-1 is responsive to glucocorticoids and this mechanism might influence neurogenesis in the hippocampus.
Tamura
Goichiro
G
University of South Dakota School of Medicine, Division of Basic Biomedical Sciences, Vermillion, SD 57069, USA.
Olson
Dawne
D
Miron
Joel
J
Clark
Timothy G
TG
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D002452:Cell Count / Q000379:methods; D045744:Cell Line, Tumor; D003001:Cloning, Molecular / Q000379:methods; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005938:Glucocorticoids / Q000494:pharmacology / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000379:methods; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012149:Restraint, Physical / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012737:Sex Factors; D013312:Stress, Physiological / Q000378:metabolism*; D013997:Time Factors; D055394:Tolloid-Like Metalloproteinases
D005938:Glucocorticoids; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D045726:Metalloproteases; D055394:Tolloid-Like Metalloproteinases; C484477:Tll1 protein, mouse