Regulation of Oxytocin Receptor Expression in Cultured Human Myometrial Cells by Fetal Bovine Serum and Lysophospholipids

Dec 19, 2002Endocrinology

Control of oxytocin receptor levels in human uterine muscle cells by animal serum and fat-related molecules

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Abstract

Oxytocin receptor (OTR) expression in human myometrium increases over 150-fold from the beginning of pregnancy to the end.

Serum starvation down-regulated OTR ligand-binding sites and mRNA levels in myometrial cells.
Restoring fetal bovine serum (FBS) increased OTR mRNA half-life by about 5-fold.
Lysophospholipids present in serum had effects similar to those of FBS on OTR expression.
Myometrial cells expressed lysophospholipid receptor mRNAs from the endothelial differentiation gene family.
G protein-coupled receptors associated with these lysophospholipids are linked to the activation of specific signaling pathways.
Inhibition of G(i/o) signaling blocked the stabilizing effects of FBS on OTR mRNA.

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Oxytocin receptor (OTR) expression in human myometrium increases over 150-fold from the beginning of pregnancy to the end. In the present studies, we examined potential mechanisms of OTR up-regulation, using myometrial cells in primary culture from women in late gestation. OTR ligand-binding sites and steady-state mRNA levels were down regulated by serum starvation, and up-regulated by restoration of fetal bovine serum (FBS). Transcriptional activity of the OTR gene was the same with or without FBS treatment, but FBS increased OTR mRNA half-life about 5-fold. Lysophospholipids (lysophosphatidic acid and sphingosine 1-phosphate), which are present in serum, had similar effects as FBS. Lysophospholipid receptor mRNAs of the endothelial differentiation gene (Edg) family (Edgs 1, 3, 4, and 5) were demonstrated in myometrial cells by RT-PCR. These G protein-coupled receptors have been shown to be coupled to G(i/o) and to mediate activation of phosphoinositol 3-phosphate kinase. Indeed, the effects of the lysophospholipids and FBS were completely blocked by pertussis toxin, a G(i/o) inhibitor. Likewise, inhibition of G(i/o) signaling by elevation of intracellular cAMP or inhibition of phosphoinositol 3-phosphate kinase blocked FBS effects on OTR mRNA stability. We do not presently understand the mechanisms of OTR up-regulation in human myometrium in vivo, but the present studies might lead to the description of mRNA-stabilizing factors whose activity can be quantified in tissue samples during pregnancy to elucidate the process of OTR up-regulation.

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Regulation of Oxytocin Receptor Expression in Cultured Human Myometrial Cells by Fetal Bovine Serum and Lysophospholipids

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