Fine temporal analysis of DHT transcriptional modulation of the ATM/Gadd45g signaling pathways in the mouse uterus.
In rodents, the uterus of a mature female undergoes changes during the uterine cycle, under the control of steroid hormones. 5alpha-Dihydrotestosterone (DHT) is recognized to play an important role in the regulation of androgen action in normal endometrium. Using microarray technology, a screening analysis of genes responding to DHT in the uterus of ovariectomized mice, has allowed us to highlight multiple genes of the ATM/Gadd45g pathway that are modulated following exposure to DHT. Two phases of regulation were identified. In the early phase, the expression of genes involved in the G2/M arrest is rapidly increased, followed by the repression of genes of the G1/S checkpoint, and by the induction of transcriptional regulators. Later, i.e. from 12 to 24 hr, genes involved in G2/M transition, cytoarchitectural and lipid-related genes are stimulated by DHT while immunity-related genes appear to be differentially regulated by the hormone. These results show that a physiological dose of DHT induces the transcription of genes promoting the cell cycle progression in mice. Profile determination of temporal uterine gene expression at the transcriptional level enables us to suggest that the DHT modulation of genes involved in ATM/Gadd45g signaling in an ATM- or p53-independent manner, could play an important role in the cyclical changes of uterine cells in the mouse uterus.
Ivanga
Mahinè
M
Oncology and Molecular Endocrinology Research Center, CHUL Research Center, CHUQ, Department of Anatomy and Physiology, Laval University, Québec, Canada.
Labrie
Yvan
Y
Calvo
Ezequiel
E
Belleau
Pascal
P
Martel
Céline
C
Pelletier
Georges
G
Morissette
Jean
J
Labrie
Fernand
F
Durocher
Francine
F
D000728:Androgens / Q000494:pharmacology; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D016000:Cluster Analysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D010052:Ovariectomy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D014599:Uterus / Q000378:metabolism*; D000097642:GADD45 Proteins
D000728:Androgens; D064007:Ataxia Telangiectasia Mutated Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D013196:Dihydrotestosterone; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; C121373:Gadd45g protein, mouse; D000097642:GADD45 Proteins; C576325:Atm protein, mouse