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Estrogen and progesterone differentially regulate UTP‐stimulated anion secretion in endometrial epithelial cells by altering expression of P2Y receptors and basolateral K + channels
Author(s) -
Palmer Melissa L.,
Schiller Katherine R.,
O’Grady Scott M.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a956-c
Subject(s) - medicine , epithelial polarity , stimulation , endocrinology , receptor , estrogen , chemistry , secretion , p2y receptor , estrogen receptor , messenger rna , biology , cell , biochemistry , purinergic receptor , cancer , breast cancer , gene
Immortalized porcine endometrial epithelial (PEG) cells were grown on Transwell membrane filters under serum free conditions and exhibited basal ENaC‐mediated Na + absorption. Apical stimulation with UTP inhibited Na + transport and activated CFTR and CaCC‐dependent anion secretion that oscillated over time. Incubation of cells with 20 nM 17β estridiol for 96 hours enhanced the magnitude and frequency of the Isc oscillations elicited by UTP. In contrast treatment with progesterone (100 nM) significantly reduced the UTP‐stimulated Isc and its subsequent oscillations. QRT‐PCR analysis revealed that PEG cells express P2Y 2 , P2Y 4 and P2Y 6 receptors, with P2Y 2 in greatest abundance. Stimulation with estrogen had no effect on P2Y 2 or P2Y 6 mRNA expression compared to serum‐free conditions, but significantly reduced P2Y 4 mRNA by more than 80%. In contrast, progesterone stimulation inhibited both P2Y 4 and P2Y 6 mRNA expression by more than 90%. Additionally, estrogen and progesterone reduced mRNA expression for KCNQ1 and SK4 K + channels present in the basolateral membrane by approximately 65%. However, UTP stimulated the activity of a basolateral K + channel that exhibited current oscillations similar to the oscillations in Isc observed in experiments with the intact epithelium. The results of the experiments demonstrate that estrogen and progesterone differentially regulate the responsiveness of PEG cells to UTP by altering the expression pattern of P2Y receptors that bind the nucleotide and basolateral K + channels that play a role in sustaining the electrical driving force for anion secretion.