The effect of relaxin on the oxytocin receptor in human uterine smooth muscle cells.
OBJECTIVE
Activation of the oxytocin receptor (OTR) induces phospholipase C induced PIP(2) turnover in the human uterus. Relaxin (RLX), a polypeptide hormone produced in the corpus luteum of pregnancy as well as in the placenta and decidua inhibits PIP(2) turnover and subsequent signaling in human myometrium. The purpose of this study was to evaluate a possible effect of RLX on OTR regulation in human uterine smooth muscle cells. Primary cultures of myometrium from term pregnant women undergoing elective caesarean section were incubated for different time periods (0-96 h) and with different concentrations of RLX [10 pg/ml-20 microg/ml]. The effects on OTR binding, mRNA and protein expression were evaluated by means of (125)I-OVT binding assay, RT-PCR and flow cytometry.


RESULTS
Prolonged RLX incubation was able to inhibit 30-40% of OTR binding while binding affinity remained unchanged. Oxytocin receptor mRNA and protein expression were down regulated by RLX about 50% and 35% respectively.


CONCLUSIONS
We report for the first time an effect of RLX on OTR regulation in human uterine myometrial cells. The above results indicate that high local uterine RLX concentrations may be involved in uterine quiescence during human pregnancy by down regulating the OTR.
Friebe-Hoffmann
Ulrike
U
Magee-Women's Research Institute, Department of Maternal-Fetal-Medicine, University of Pittsburgh, 204 Craft Avenue, PA 15213, USA. ufriebehoffmann@yahoo.com
Baston
Dunja M
DM
Chiao
Jye-Ping
JP
Winebrenner
Liza D
LD
Krüssel
Jan S
JS
Hoffmann
Thomas K
TK
Hirchenhain
Jens
J
Rauk
Phillip N
PN
D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008954:Models, Biological; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011869:Radioligand Assay; D018045:Receptors, Oxytocin / Q000235:genetics* / Q000378:metabolism; D012065:Relaxin / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D012065:Relaxin