Disease relevance of OXTR

• Plasma concentrations of the oxytocin receptor blocking agent Atosiban were measured at 2, 4, 10, 15 and 20 min after injection of 5, 10, 20 and 50 micrograms Atosiban/kg body weight in six dairy cows [1].

High impact information on OXTR

• 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 [2].
• Oxytocin receptor (OTR) expression in human myometrium increases over 150-fold from the beginning of pregnancy to the end [2].
• In the present studies, we examined potential mechanisms of OTR up-regulation, using myometrial cells in primary culture from women in late gestation [2].
• 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 [2].
• [3H]OT binding and specificity, localization of immunoreactive (ir) OTR, OTR messenger RNA, and OT-induced release of PGF2alpha were determined [3].

Biological context of OXTR

• The oxytocin receptor (OTR) is expressed in the cow uterus at high levels at estrus and at term of pregnancy [4].
• Approximately 3200 base pairs of the upstream region of the bovine OTR gene were cloned and analyzed using a combination of bioinformatic, electrophoretic mobility shift (EMSA), and transfection analyses [4].
• The gene for the bovine oxytocin receptor has been sequenced using a combination of clones derived from a bovine endometrial cDNA library from estrus and a bovine genomic DNA library, with confirmation of structure using reverse transcription PCR programmed by term myometrial RNA [5].
• All regions of cervix from cows at estrus had high concentrations of OTR; in the luteal phase, all were sharply down-regulated [6].
• Changes in uterine oxytocin receptor concentrations throughout the estrous cycle of the cow [7].

Anatomical context of OXTR

• E2 did, however, increase (P<0.001) the OTR number in cells cultured with P4 for 21 days, whereas it inhibited OTR in cells cultured for 10 days [8].
• In vitro experiments on oviducts of cyclic cows were undertaken to study: (1) the content of dopamine (DA), noradrenaline (NA) and adrenaline (A) in infundibulum, ampulla and isthmus, (2) the concentration of oxytocin receptors (OTR) in oviductal tissues and (3) the motility of ampulla and isthmus [9].
• RESULTS: IFNtau acts on uterine epithelium to suppress transcription of the genes for estrogen receptor and oxytocin receptor [10].
• The ir-OTR was localized in luminal epithelial cells of endometrium and cervical mucosa, most of which were ir positive, whereas in myometrium, clusters of ir-OTR-positive cells were found among large numbers of ir-OTR-negative cells [3].
• On Days 7-17, the OTR mRNA signals in both mucosa and muscle were very faint or nondetectable [6].

Associations of OXTR with chemical compounds

• These data show that E2 can stimulate PGF2 alpha secretion by increasing OTR expression in bovine endometrial cells in vitro, but only after exposure to P4 [8].
• The molar ratio of estrone and estradiol-17 beta to progesterone rose from less than 0.01 to 4.4 during labor, and was correlated with oxytocin receptor concentrations in endometrium (r = 0.5160, p < 0.001), but not those in myometrium (r = 0.0122) [11].
• When the granulosa cells obtained from small follicles were cultured in Dulbecco's Modified Eagle's Medium and Ham's F-12 medium (1:1 [v:v]) with 10% calf serum up to 72 h, as the period of culture was prolonged, the concentration of OT receptor decreased with increases of progesterone and OT release in the medium [12].
• OT significantly increased PGF2alpha and PGE2 secretion at all time points (p < 0.01), while rbIFN-tau inhibited the OT-induced PG production and reduced OT receptor binding in a time-dependent manner [13].
• The objective of the present study was to determine, whether this effect of mifepristone was due to changes in prostaglandin synthesis and/or OTR [14].

Physical interactions of OXTR

• In contrast, the levels of oxytocin receptor mRNA and specific binding sites for oxytocin in granulosa cells had decreased significantly at 12 and 24 h post-GnRH [15].

Regulatory relationships of OXTR

• The oxytocin-induced membrane changes were suppressed when oocytes were pretreated with an oxytocin receptor antagonist [16].
• Interferon-tau (IFN tau) acts locally on the endometrium to suppress estrogen and oxytocin receptor expression and block luteolysis in ruminants [17].

Other interactions of OXTR

• To determine the mechanism of action of E2, COX-1 and COX-2 were measured by Western blotting and OTR number was measured by saturation analysis [8].
• Oxytocin induces prostaglandin F2 alpha release in pregnant cows: influence of gestational age and oxytocin receptor concentrations [18].
• A sensitive RNase protection assay was developed to detect transcripts encoding the oxytocin receptor [19].
• A series of experiements was performed to determine whether proteins produced by the sheep conceptus (oCSP) during the time of maternal recognition of pregnancy or bovine recombinant interferon alpha 1-1 (brIFN) decrease oxytocin receptor concentrations in the endometrium of cyclic or ovariectomized progesterone-treated ewes [20].
• Oxytocin receptor, oestrogen receptor alpha and progesterone receptor mRNAs were localized by in situ hybridization, and localization of oestrogen receptor and progesterone receptor was confirmed by immunocytochemistry [21].

Analytical, diagnostic and therapeutic context of OXTR

• Cellular localization of OTR protein was determined by immunohistochemistry [6].
• With use of a reverse transcriptase polymerase chain reaction analysis, expression of OT receptor mRNA was detected in granulosa cells obtained from both small and mature follicles [12].
• Observation of one versus two binding sites related neither to the assay conditions nor to the state of the individual CL used for the cell culture and therefore appeared to reflect individual variation within the OT receptor population [22].
• In situ hybridization to ovine mRNA encoding the oxytocin receptor and autoradiographic studies using the 125I-labelled oxytocin antagonist d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]-vasotocin both showed that the large amount of oxytocin receptor message and binding sites in the endometrium of the isolated horn were localized in the luminal epithelium [23].
• OTR protein was measured by autoradiography with iodinated oxytocin antagonist and ER and PR protein was detected by immunocytochemistry [24].

References