“…The animals were subsequently killed at term before labor (not in labor [NIL] ϭ Days 140-145; n ϭ 5); ewes in early labor (EL ϭ Days 143-149; n ϭ 6); and ewes in active labor (L ϭ Days 145-149; n ϭ 6). Determination of progression of labor was assessed during the last 6 h before the animal was killed and was based on the criteria discussed by Lye et al [17]. Animals NIL displayed long wave contractions lasting 5-8 min (contracture) at a frequency of three or four contractures in 2 h on their electromyogram traces with a parallel slow wave rise of the intrauterine pressure (IUP) of Ͻ5 mm Hg on average.…”
Recent evidence suggests that ovine placental output of prostaglandin (PG) E2 rises through late gestation partly because of a direct effect of cortisol on PGH2 synthase 2 (PGHS-2) expression and activity within trophoblast tissue. Synthesis of PGE2 is also dependent, however, on PGE2 synthase (PGES), which converts PGH2 to PGE2. We hypothesized that PGES is expressed in the ovine placenta, and that, similar to PGHS-2, expression increases through gestation and is regulated positively by cortisol. Placental tissues from pregnant ewes in mid and late gestation, at term, and during early and active labor were analyzed to determine the gestational profile of PGES. The regulation of PGES expression was assessed in placental tissues from pregnant ewes in which intrafetal cortisol infusion was administered in late gestation, in the presence or absence of an aromatase inhibitor, to block the cortisol-stimulated rise in estradiol. Expression of PGES was analyzed by in situ hybridization, Western blot analysis, and immunohistochemistry. In the placentome, PGES localized to fetal trophoblast cells and endothelial cells in maternal blood vessels, consistent with its contribution to the rise in placental PGE2 output toward the onset of labor and with a role of PGE2 in the local regulation of uteroplacental blood flow, respectively. Expression of PGES mRNA and protein increased with gestation. However, there was no significant further change with labor or during cortisol infusion in the presence or absence of a rise in fetal plasma estradiol, in contrast to reported changes in PGHS-2. These results suggest that PGES is not coregulated with PGHS-2 in the sheep placenta at term. The progressive increase in PGES, however, likely contributes to the rise in circulating PGE2 in the fetus in late pregnancy.
“…The animals were subsequently killed at term before labor (not in labor [NIL] ϭ Days 140-145; n ϭ 5); ewes in early labor (EL ϭ Days 143-149; n ϭ 6); and ewes in active labor (L ϭ Days 145-149; n ϭ 6). Determination of progression of labor was assessed during the last 6 h before the animal was killed and was based on the criteria discussed by Lye et al [17]. Animals NIL displayed long wave contractions lasting 5-8 min (contracture) at a frequency of three or four contractures in 2 h on their electromyogram traces with a parallel slow wave rise of the intrauterine pressure (IUP) of Ͻ5 mm Hg on average.…”
Recent evidence suggests that ovine placental output of prostaglandin (PG) E2 rises through late gestation partly because of a direct effect of cortisol on PGH2 synthase 2 (PGHS-2) expression and activity within trophoblast tissue. Synthesis of PGE2 is also dependent, however, on PGE2 synthase (PGES), which converts PGH2 to PGE2. We hypothesized that PGES is expressed in the ovine placenta, and that, similar to PGHS-2, expression increases through gestation and is regulated positively by cortisol. Placental tissues from pregnant ewes in mid and late gestation, at term, and during early and active labor were analyzed to determine the gestational profile of PGES. The regulation of PGES expression was assessed in placental tissues from pregnant ewes in which intrafetal cortisol infusion was administered in late gestation, in the presence or absence of an aromatase inhibitor, to block the cortisol-stimulated rise in estradiol. Expression of PGES was analyzed by in situ hybridization, Western blot analysis, and immunohistochemistry. In the placentome, PGES localized to fetal trophoblast cells and endothelial cells in maternal blood vessels, consistent with its contribution to the rise in placental PGE2 output toward the onset of labor and with a role of PGE2 in the local regulation of uteroplacental blood flow, respectively. Expression of PGES mRNA and protein increased with gestation. However, there was no significant further change with labor or during cortisol infusion in the presence or absence of a rise in fetal plasma estradiol, in contrast to reported changes in PGHS-2. These results suggest that PGES is not coregulated with PGHS-2 in the sheep placenta at term. The progressive increase in PGES, however, likely contributes to the rise in circulating PGE2 in the fetus in late pregnancy.
“…Progression of labor was assessed during the last 6 h before death based on the criteria discussed by Lye et al [25]. NIL animals displayed long-wave myometrial contractions lasting 5-8 min (contracture) at a frequency of ϳ3-4 per 2 h on their EMG traces with a parallel slow-wave rise of the IUP of Ͻ 5 mm Hg on average [26].…”
We examined whether spontaneous parturition in sheep was associated with tissue-specific changes in prostaglandin H(2) synthase-2 (PGHS-2) expression and/or with altered expression of myometrial EP and FP receptors. Placental and uterine tissues were collected from three groups of chronically catheterized sheep in relation to term spontaneous labor: late pregnancy, not in labor; early labor; and active labor. Expression of PGHS-2 mRNA and protein was determined by in situ hybridization, Western blotting, and immunohistochemistry. Semiquantitative reverse transcription-polymerase chain reaction was used to assess the presence of and changes in prostaglandin (PG) receptor subtypes. In placenta, PGHS-2 mRNA and protein localized to trophoblast uninucleate cells and tended to increase with early labor. PGHS-2 mRNA and protein localized to endometrial epithelium and to myometrium, where PGHS-2 protein levels rose in active labor tissues. Concentrations of PGE(2) in fetal plasma rose progressively with labor, whereas 13,14-dihydro-15-keto-PGF(2alpha) in maternal plasma increased significantly only in active labor. Messenger RNA encoding four EP receptor subtypes and FP receptor were present in myometrium, but levels did not change with labor. We suggest that spontaneous labor in sheep is associated with a progressive increase in PGHS-2 expression in a temporal and tissue-specific manner from trophoblast to maternal tissues, rather than alteration in PG receptor gene expression.
“…The effectiveness of these agents is, however, limited due to a relatively rapid development of tachyphylaxis (Lye et al 1992), and consequently the incidence of preterm delivery (Hemminki & Starfield 1978) as well as perinatal morbidity and mortality (The Canadian Preterm Labor Investigators Group 1992) has remained unchanged during several years. Tachyphylaxis denotes the progressive loss of a cellular response upon continued stimulation with a given agonist.…”
The effects of in vivo treatment with estrogen and progesterone on isoproterenol-induced uterine relaxation and 2 -adrenoceptor ( 2 AR) mRNA production in nonpregnant rat myometrium were investigated. Whether homologous myometrial desensitization of 2 AR function was dependent on or modulated by the two steroids was also examined.Estrogen treatment alone or in combination with progesterone reduced maximal relaxation (E max ) of isolated uterine strips subsequently challenged with isoproterenol whereas progesterone alone had no effect on this parameter. The reduction was accompanied by an enhanced 2 AR mRNA concentration. The concentration of isoproterenol giving half-maximal relaxing response (EC 50 ) increased following estrogen treatment and this effect was curbed by progesterone.Isoproterenol had no effect on 2 AR transcription irrespective of the steroid regimes employed. E max of isolated uterine strips was reduced following prolonged in vivo treatment with isoproterenol but the effect was found only when estrogen alone was administered concomitantly. Finally, in vivo treatment with isoproterenol increased EC 50 of uterine strips subsequently stimulated with isoproterenol in vitro. This effect was independent of steroid treatment.We conclude that homologous desensitization of 2 AR function in non-pregnant rat myometrium in terms of sensitivity (EC 50 ) is independent of sex steroids but in terms of maximal response (E max ) occurs only in the presence of estrogen. We speculate whether progesterone withdrawal in connection with the well-known estrogen dominance at rat parturition may strengthen the desensitization induced by 2 AR activation and thus contribute to the transformation of the uterus from a quiescent to a highly contractile organ.
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