Desensitization of oxytocin receptors in human myometrium

In the present study, we investigated the possible mechanisms by which oxyt ocin might regulate oxytocin receptor (OTR) density, Exposure of cultured m yometrial cells to oxytocin for a prolonged period caused desensitization: the steady-state level of oxytocin binding was 210 x 10(3) binding sites/ce ll, but this was time-dependently reduced to 20.1 x 10(3) sites/cell by exp osing the cells to oxytocin for up to 20 h. In contrast, Western blotting d ata showed that the total amount of OTR protein was not affected by oxytoci n treatment for up to 24 h, Flow cytometry experiments demonstrated that OT Rs were not internalized during this treatment. However, RNase protection a ssays and Northern analysis showed that in cultured myometrial cells OTR mR NA was reduced by oxytocin treatment to reach a new low steady-state concen tration, Analysis of this mRNA in myometrial biopsies from 17 patients unde rgoing emergency Caesarean section showed how it decreased with advancing l abour Samples obtained after 12 h of labour contained approximately 50 time s less OTR mRNA than samples obtained from patients in labour for less than 12 h. We speculate that this decrease in OTR mRNA represents in-vivo OTR d esensitization.