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This Article Full Text Full Text (PDF) All Versions of this Article: 287/3/E439    most recent 00275.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Mitchell, J. A. Articles by Lye, S. J. Search for Related Content PubMed PubMed Citation Articles by Mitchell, J. A. Articles by Lye, S. J.

Mechanical stretch and progesterone differentially regulate activator protein-1 transcription factors in primary rat myometrial smooth muscle cells

¹Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto M5G 1X5; ²Institute of Medical Science and ³Department of Obstetrics & Gynecology, University of Toronto, Toronto M5S 1A1; and ⁴University Health Network, Toronto General Research Institute, Toronto, Ontario M5G 2C4, Canada

Submitted 19 June 2003 ; accepted in final form 27 April 2004

During pregnancy, stretch of the uterus, imposed by the growing fetus, is an important signal for the induction of genes involved in the onset of labor. In this study, the expression of activator protein-1 (AP-1) family mRNAs in response to in vitro stretch was investigated in myometrial cells. Rat primary myometrial smooth muscle cells were plated onto collagen I-coated Flex I culture plates and subjected to 25% static stretch on day 4 of culture. Static stretch induced an increase in the expression of c-fos, fosB, fra-1, c-jun, and junB. The expression of both c-fos and junB was maximally induced at 30 min by static stretch. The peak induction for fosB and c-jun occurred at 1 h, whereas the peak of fra-1 induction occurred between 1 and 2 h after application of stretch. Treatment of myometrial cells with progesterone (100 nM, 400 nM, 1 µM) for 1 or 6 h before the application of static stretch did not affect the magnitude of the c-fos response. However, 24 h of progesterone exposure reduced the magnitude of c-fos and fosB stretch induction at both the 400 nM and 1 µM doses. These data indicate that several members of the AP-1 family are stretch-responsive genes in myometrial smooth muscle cells. This response can be attenuated by pretreatment with progesterone; however, the requirement for longer pretreatment times suggests that the inhibitory actions of progesterone do not occur through a direct action of the progesterone receptor within the promoter regions of AP-1 genes.

fos; jun; myometrium; uterus

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