High impact information on OTR

• Membranes from endometrial tissue of ovariectomized hormone-treated ewes were preincubated in the presence of P4 for 1 h followed by OT receptor analysis [1].
• ERalpha, Hsp90, OTR, and PGHS2 mRNA were all significantly up-regulated during betamethasone-induced labor (P < 0.01) in gravid and nongravid horn myometrium [2].
• We also examined the regulatory effects of estrogen and progesterone on OTR mRNA expression in ovariectomized nonpregnant sheep [2].
• Mechanical stretch appears largely responsible for increased OTR mRNA and to a lesser degree PGHS2 mRNA [2].
• In the endometrium, nimesulide produced a decrease in ER and OTR mRNA (P < 0.05) compared with vehicle infused animals, but the changes in Hsp 90 and 70 mRNA fell outside the level of significance [3].

Biological context of OTR

• The results indicate that induction of luteolysis by E in control ewes involved sequential increases in endometrial ER mRNA and ER protein in the epithelium that preceded maximal increases in OTR density [4].
• Results suggest that the antiluteolytic action of IFNtau is to suppress transcription of the ER gene by a negative-acting transcriptional mechanism which prevents estrogen-induced increases in OTR gene expression in the endometrium [5].
• There are no studies in sheep in which the physical properties and histological distribution of OTR are evaluated in relation to parturition [6].
• Increased OTR and its mRNA expression in the myometrium and endometrium were correlated with the occurrence of myometrial contractions [6].
• Collectively, these data suggest that in cycling ewes, exposure of the uterus to increased concentrations of E2 or P4 causes down-regulation of OTR as a consequence of suppression of the OTR gene [7].

Anatomical context of OTR

• These PGF pulses are produced by the endometrial lumenal epithelium (LE) and superficial ductal glandular epithelium (sGE) in response to binding of pituitary and/or luteal oxytocin to oxytocin receptors (OTR) and liberation of arachidonic acid, the precursor of PGF [8].
• In this study, steady-state levels of ER mRNA and transcription rates of the ER and OTR genes were two-fold lower in the endometrium of pregnant as compared to cyclic ewes on day 15 [5].
• OTR was also demonstrated by immunocytochemistry in the smooth muscle of myometrial blood vessels [6].
• We also examined the distribution of OTR mRNA and protein expression in the intact myometrium and endometrium and in individual cultured cells using in situ hybridization and immunocytochemistry [6].
• OTR mRNA was localised to the placentome capsule at days 34-40, remaining high at day 45 and declining to basal levels by days 132-137 [9].

Associations of OTR with chemical compounds

• In myometrium after nimesulide infusion, OTR and Hsp 70 mRNA decreased significantly (P < 0.05) compared with vehicle infused animals, but the decrease in Hsp 90 and ER mRNA fell outside the level of significance [3].
• IFNtau acts as an antiestrogen on the endometrium to suppress increases in estrogen receptor (ER) and oxytocin receptor (OTR) gene expression which prevents pulsatile production of prostaglandin F2alpha and regression of the corpus luteum or luteolysis [5].
• Intrauterine administration of recombinant ovine IFNtau suppresses expression of endometrial estrogen receptor (ER) and oxytocin receptor (OTR) in the luminal and superficial glandular epithelia to abrogate the production of luteolytic prostaglandin F(2alpha) (PGF(2alpha)) pulses [10].
• However, roIFN-tau did suppress endometrial ER expression and OTR formation in ewes regardless of steroid treatment [11].
• The functional properties of the expressed OTR were determined by measuring oxytocin-induced phosphoinositide (PI) hydrolysis [12].

Other interactions of OTR

• Results suggest that IFNtau acts directly on the LE and sGE during pregnancy to sequentially induce IRF-1 and then IRF-2 gene expression, which is correlated temporally with an absence of ER and OTR [13].
• Tamoxifen, the antiestrogen most widely used in medicine, was tested in ewes to determine whether it antagonizes oestradiol up-regulation of ER, PR, and other genes reported to be oestrogen-modulated (c-fos, oxytocin receptor (OTR), glyceraldehyde phosphate dehydrogenase (GAPDH), and apolipoprotein AI (apo AI)) in endometrium and liver [14].
• This study investigated the localisation of OTR mRNA in the ovine placentome throughout gestation and related this to expression patterns for the putative regulatory agents aromatase, oestradiol receptor, progesterone receptor and oxytocin [9].
• In intact cyclic ewes intrauterine infusion of conceptus secretory proteins results in the suppression of both endometrial oxytocin receptor concentrations and oxytocin-induced prostaglandin F2 alpha release [15].
• Endometrial IFN receptors are present, and trophoblast IFN decreases expression of endometrial oxytocin receptor and increases expression of endometrial beta 2-microglobulin, MHC class I antigens and Mx (a mediator of IFN antiviral activity) only in the pregnant horn of pregnant ewes with a transected uterus [16].

Analytical, diagnostic and therapeutic context of OTR

• Western blot analysis of myometrial and endometrial extracts revealed a major form of OTR with an approximate molecular mass of 66 kDa [6].
• Both immunocytochemistry and in situ hybridization localized OTR and its mRNA in myometrial cells and glandular cells of the endometrium [6].
• ER, OTR, Hsp 70 and 90, cPLA2, and PGHS-2 messenger RNA (mRNA) abundance in myometrium, endometrium, and PGHS-2 in placenta were quantified by Northern blot analysis [3].
• The entire coding region of an ovine endometrial oxytocin receptor (OTR) cDNA was generated by PCR, subcloned into the SV40 major late promoter expression vector pSVLJ and transiently expressed in Cos-7 cells [12].

References