Molecular Human Reproduction, Vol 4, 33-39, Copyright © 1998 by Oxford University Press
M Breuiller-Fouche, V Heluy, T Fournier, E Dallot, MC Vacher-Lavenu and F Ferre
Endothelin-1 (ET-1) exhibits vasoconstricting and growth-promoting
properties in vascular smooth muscle. Whether ET-1 has mitogenic properties
in uterine smooth muscle cells, and which ET receptor subtype mediates this
response, is unknown. The present study was undertaken to examine the
proliferative potential of the ET family on human myometrial cells in
culture. ET-1 stimulated DNA synthesis and proliferation of myometrial
cells. The absence of a stimulating effect of endothelin-3 (ET-3) or the
ETB agonist sarafotoxin 6c (S6c) was observed. The proliferative effect of
100nM ET-1 was blocked by the two ETA antagonists (BQ 123 and FR 139317),
whereas the ETB antagonist IRL 1038 was ineffective. These data indicated
that ET-1-induced DNA synthesis was mediated only by the ETA receptor
subtype. Pertussis toxin (PTX) pretreatment completely abolished this
effect, indicating that this pathway was coupled to the ETA receptor via
the Gi protein family. PTX treatment partially decreased serum-induced DNA
synthesis. This suggests that some factors from serum may operate via the
G- protein in initiation of mitogenesis. Insulin-like growth factors
(IGFs), epidermal growth factor (EGF) and insulin were found to be mitogens
in the absence of serum, and they had no potentiating effect on
ET-1-induced DNA synthesis. In the presence of 0.5% serum, EGF alone caused
a weak increase in DNA synthesis, while all the growth factors were able to
reduce the proliferative effect of ET-1. These findings on human myometrial
cells in culture raise the possibility that, under certain conditions, ET-1
may function as a positive or as a negative modulator of smooth muscle
proliferation.
JOURNAL ARTICLE
Role of endothelin-1 in regulating proliferation of cultured human uterine smooth muscle cells
Institut National de la Sante et de la Recherche Medicale, U.361, Universite Rene-Descartes, Paris, France.
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