research day - University of Toronto Department of Obstetrics and ...

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ABSTRACT #P-E1
THE ROLE OF ANDROGEN SIGNALING IN THE ONSET OF LABOR. (WORK-IN-
PROCESS)
Yunqing Li [G] (1,2), Oksana Shynlova (1), Xuesen Dong (4), Stephen J Lye (1,2,3).
(1)Samuel Lunenfeld research Institute, Mount Sinai Hospital, Department of (2) Physiology and
(3)Obstetrics & Gynaecology, University of Toronto, (4)Prostate Center at Vancouver General
Hospital, University of British Columbia.
It was reported earlier that plasma levels of androgen during pregnancy in rats show the similarity
to those of progesterone. The decrease of androgen levels in the circulation near term (analogous to
the decrease of progesterone levels) may facilitate up-regulation of contraction associated protein
(CAP) gene expression in the myometrium. The androgen receptor (AR) is a member of the
nuclear receptor super-family that functions as a ligand-dependent transcription factor that can
regulate the expression of target genes. Our preliminary data show that AR was able to suppress
transcriptional activity of Cx43 promoter in vitro. Thus, we hypothesize that the AR, similar to
the progesterone receptor (PR), is able to suppress CAP genes (i.e. Cx43) in vivo in the pregnant
rat myometrium.
Objective: (1) To study the protein expression of AR in rat myometrium throughout gestation; (2)
To develop a new rat preterm labor model using Casodex, a well-known inhibitor of AR as to
investigate whether androgen signaling regulate the expression of CAP genes in vivo.
Methods: (1) Myometrial tissues were collected from pregnant rats on gestational days 8, 10, 14,
15, 19, 21, 23 (day of labor) and day 1 postpartum (n = 4 at each time point) for Western blot
analysis of AR expression.
(2) Pregnant animals (gestational day 17) were split into two groups. Group 1 consisted of 8
animals treated with subcutaneous injections of Casodex (100 mg/kg/day or 50 mg/kg/day) and
group 2 consisted of 8 animals treated with vehicle (DMSO). For each group, uterine tissues are
collected after 24 hours (4 animals) and 48 hours (4 animals) and processed for
immunohistochemical and biochemical analysis.
Results: Densitometric analysis revealed high levels of AR expression throughout early and midpregnancy
and a significant decrease with the approach of term and during labor (p < 0.05). This
data confirms that protein gestational profile for AR is similar to that of PR. We are currently in
process of developing the Casodex-induced rat preterm labor model.
Conclusions: Our preliminary data suggest that during pregnancy androgen signaling may play an
important role by repressing labor-related genes during first half of gestation. At term, when
progesterone and androgen plasma levels decrease and both receptors (PR and AR) are downregulated
in the myometrium, the suppression of CAP genes is abolished.
Funded by: CIHR #42378