Effects of PGF2α on the Expression of Uterine Activation Proteins in Pregnant Human Myometrial Cells From Upper and Lower Segment

May 17, 2013The Journal of clinical endocrinology and metabolism

PGF2α’s effects on uterine activation proteins in upper and lower muscle cells of pregnant human uterus

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Abstract

PGF2α dose dependently increased levels of connexin 43 and prostaglandin endoperoxide synthase-2 while decreasing prostaglandin F2α receptor in upper and lower segments of cultured human myometrial cells.

PGF2α increased connexin 43 and prostaglandin endoperoxide synthase-2 in both upper and lower myometrial segments.
In the lower segment, PGF2α increased oxytocin receptor levels but decreased them in the upper segment.
Knockdown of the prostaglandin F2α receptor eliminated the effects of PGF2α on prostaglandin endoperoxide synthase-2 and oxytocin receptor, but not on connexin 43.
A specific antagonist of the prostaglandin F2α receptor reversed PGF2α's actions on uterine activation proteins, except for connexin 43 in the lower segment.
The presence of interleukin-1β enhanced PGF2α's stimulatory effects and reversed its inhibitory effect on the prostaglandin F2α receptor.

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CONTEXT: The lower and upper segments of the uterus may play different roles in the process of parturition. The switch from pregnancy to delivery involves changes in expression of uterine activation proteins (UAPs). Prostaglandin (PG) F2α has multiple and complex roles in the birth process in addition to its vital contractile role.

OBJECTIVE: The purpose of this study was to investigate whether PGF2α regulates the expression of UAPs in human myometrium and to compare PGF2α actions in lower and upper segments.

DESIGN: Cultured human myometrial cells from upper and lower segments were treated with PGF2α. Western blotting was used to determine the levels of connexin 43 (CX-43), prostaglandin endoperoxide synthase-2 (PTGS-2; cyclooxygenase-2), oxytocin receptor (OTR), and PGF2α receptor (PTGFR) in the cells. The small interfering RNA approach was used to knock down PTGFR.

RESULTS: PGF2α dose dependently increased CX-43 and PTGS-2 while decreasing PTGFR in upper and lower segments. PGF2α increased OTR in the lower segment while decreasing it in the upper segment. PGF2α lost its effects on PTGS-2 and OTR in PTGFR knockdown cells, but its effect on CX-43 remained. AL8810, a specific antagonist of PTGFR, reversed the actions of PGF2α on UAPs except for CX-43 in the lower segment. Indomethacin reversed the PGF2α-induced effects on CX-43 and PTGS-2, but it did not alter PGF2α-induced PTGFR and OTR expression. The stimulatory effects of PGF2α were enhanced in the presence of IL-1β, which reversed the inhibitory effect of PGF2α on PTGFR.

CONCLUSION: PGF2α regulates UAPs in both upper and lower segment cells through either direct or indirect pathways, indicating that PGF2α uniquely participates in uterine preparation for the onset of labor.

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Effects of PGF2α on the Expression of Uterine Activation Proteins in Pregnant Human Myometrial Cells From Upper and Lower Segment

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