EVIDENCE FOR A POSSIBLE FOETAL CONTROL OF PROSTAGLANDIN RELEASE FROM THE PREGNANT RAT UTERUS IN VITRO

1975 ◽  
Vol 65 (3) ◽  
pp. 429-437 ◽  
Author(s):  
M. J. PARNHAM ◽  
J. M. SNEDDON ◽  
K. I. WILLIAMS

SUMMARY The release of prostaglandin-like material and the spontaneous contractions of individual horns from the pregnant rat uterus in vitro have been studied on day 22 of pregnancy – the expected day of delivery. Removal of foetuses (retaining placentae in utero) from one or both uterine horns on day 16 or 17 significantly reduced prostaglandin F release and spontaneous activity. Rats which had been made unilaterally pregnant after ligation of one uterine horn, exhibited a decrease in prostaglandin F output from both horns. Uterine activity and prostaglandin release were increased in quiescent uteri by the addition of arachidonic acid (5 μg/ml) or phospholipase A (160 mu./ml); these effects were abolished by indomethacin (20 μg/ml). However, the stimulation of uterine activity by PGF2α (30–60 ng/ml) was not affected by indomethacin. It is concluded that the release of prostaglandins from the pregnant rat uterus in vitro at term is related to the presence of viable foetuses.

1974 ◽  
Vol 60 (2) ◽  
pp. 343-351 ◽  
Author(s):  
P. J. HARNEY ◽  
J. M. SNEDDON ◽  
K. I. WILLIAMS

SUMMARY The output of prostaglandin-like material and the spontaneous contractions of the pregnant rat uterus in vitro have been studied during the last 6 days of pregnancy and for 3 days post partum. Both prostaglandin release and uterine activity were minimal on days 17–18 of pregnancy but both parameters gradually increased, reaching a peak on day 22, the expected day of delivery. Post partum both uterine prostaglandin release and spontaneous activity declined. Progesterone (25 mg, i.m.) given to rats from days 16–21 of pregnancy did not alter uterine activity or prostaglandin output when compared with uteri taken on day 22 from animals which had received ethyl oleate over the same period. On day 22 the spontaneous activity of uteri in vitro taken from animals ovariectomized on day 17 was very low compared with that seen in preparations from sham-operated controls, although prostaglandin release in these groups was not significantly different. Oestrogen (1 μg, i.m.) was given to one group of ovariectomized animals on days 19 and 20; uterine activity was determined on day 21 of pregnancy and found to be of greater intensity and amplitude than that seen in an ovariectomized control group. Prostaglandin output was similar in these groups. Thus although exogenous progesterone and oestrogen do not influence uterine prostaglandin release at term, oestrogen appears essential for the occurrence of spontaneous contractions. It is concluded that, in the pregnant rat uterus in vitro, prostaglandin release may contribute to uterine activity but oestrogen is essential for this to become apparent.


1992 ◽  
Vol 134 (3) ◽  
pp. 415-NP ◽  
Author(s):  
V. Paspaliaris ◽  
S. J. Vargas ◽  
M. T. Gillespie ◽  
E. D. Williams ◽  
J.A. Danks ◽  
...  

ABSTRACT Classical pharmacological studies have shown that oestrogen dominance in humans and other animals can increase the responsiveness of the uterus to many locally acting peptides. Parathyroid hormone-related protein (PTHrP) has been shown to be expressed in the pregnant and non-pregnant rat uterus and exogenous PTHrP is known to relax uterine contraction in vitro. We investigated whether oestrogen dominance can influence the responsiveness of the uterine horn to PTHrP, and further studied the localization of PTHrP mRNA and protein in the rat uterine horn using in-situ hybridization and immunohistochemistry. Exogenous PTHrP(1–34) inhibited spontaneous and electrically induced contractions in uteri isolated from non-cycling rats. Pretreatment of non-cycling rats with oestradiol-17β increased uterine sensitivity to PTHrP: EC50 values for inhibition of spontaneous contractions by PTHrP were 0·33 nmol/l, 1·1 nmol/l, 2·6 nmol/l and 7800 nmol/l in uteri from animals treated for 2 days with oestradiol-17β alone, 2 days with oestradiol-17β+1 day progesterone, 1 day with oestradiol-17β alone and in untreated rats respectively. Similar EC50 values were obtained for electrically stimulated uteri. In agreement with these findings, uterine horns from cycling rats in pro-oestrous and oestrous phases of the cycle showed a higher responsiveness to PTHrP(1–34) when compared with uterine horns taken from rats in metoestrus and dioestrus. PTHrP mRNA and protein were detected in the endometrial epithelium lining of the lumen and the endometrial glands, as well as in the myometrium of rats which were either pretreated for 2 days with oestradiol-17β or untreated. This study suggests that PTHrP may act in an autocrine and/or paracrine manner to modulate uterine motility and function. Journal of Endocrinology (1992) 134, 415–425


1978 ◽  
Vol 76 (1) ◽  
pp. 111-121 ◽  
Author(s):  
M. D. MITCHELL ◽  
A. P. F. FLINT

SUMMARY A technique for the continuous superfusion of small tissue samples in vitro has been applied to the study of prostaglandin production by ovine intra-uterine tissues. Basal and oxytocin-stimulated production of prostaglandins was studied at 120–125 days of pregnancy and after dexamethasone-induced delivery. In general, the relative rate of prostaglandin production by tissues was: foetal cotyledon = maternal cotyledon>myometrium and in quantitative order the prostaglandins produced were prostaglandin E (PGE) > prostaglandin F (PGF) = 13,14-dihydro-15-oxo-prostaglandin F (PGFM). Considerable variation was found between the rates of prostaglandin production in individual sheep. Oxytocin had no effect on the production of prostaglandins by tissues obtained before labour but myometrium and maternal cotyledon obtained at delivery exhibited a significant increase in production of PGE and PGF (though not PGFM) in response to oxytocin. Administration of arachidonic acid increased the production of PGE and PGF by the foetal cotyledon.


Blood ◽  
1990 ◽  
Vol 76 (9) ◽  
pp. 1838-1844 ◽  
Author(s):  
J Maclouf ◽  
RC Murphy ◽  
PM Henson

Abstract The ability of different cell types to cooperate in the metabolism of reactive intermediates of arachidonic acid such as leukotriene A4 (LTA4) is currently receiving considerable attention. Of critical importance is the demonstration that transfer of LTA4 could occur under conditions when relatively low amounts of LTA4 are produced such as would be expected for in vitro receptor-mediated stimulation. Stimulation of human neutrophils with a combination of chemotactic factor (formyl-methionyl-leucyl-phenylalanine, FMLP) and phagocytosable particles (opsonized zymosan) resulted in little production of LTC4 alone, but measurable quantities appeared when platelets were coincubated. When these agonists were added to platelets alone in the absence of neutrophils, no LTC4 was produced. In the presence of stimulated neutrophils, the final synthesis of LTC4 was shown to occur within the platelets (from neutrophil-derived LTA4) by experiments using platelets that had been prelabeled with 35S-cysteine to label intracellular platelet glutathione. Other 35S-labeled sulfidopeptide leukotriene metabolites were also produced in this coincubation of neutrophils and platelets. The observed synergy between FMLP and opsonized zymosan in the production of LTC4 when neutrophils and platelets were coincubated may involve priming the neutrophil for LTA4 production. Activation of platelets or endothelial cells with thrombin did not alter the capacity of either cell to convert exogenously added LTA4 into LTC4. This would support the suggestion that even when platelets are activated they retain their capacity to metabolize LTA4 into LTC4. Finally, previous exposure of the platelets to LTA4 did not affect subsequent metabolism of arachidonic acid by the cyclooxygenase pathway to thromboxane A2 (TXA2) except at very high concentration of LTA4. These results suggest that cell-cell interactions may be critical determinants of the profile of eicosanoids produced in physiologic and pathophysiologic circumstances. In particular, we believe that both endothelial cells and platelets can, together with neutrophils, contribute relatively large amounts of sulfidopeptide leukotrienes to inflammatory and thrombotic events. These cell-cell interactions are aspirin-insensitive; therefore, aspirin-treated platelets are capable of synthesizing the vasoconstrictor LTC4 from neutrophil LTA4 at a time when they can no longer produce thromboxane.


1991 ◽  
Vol 130 (1) ◽  
pp. 21-32 ◽  
Author(s):  
A. M. Cowell ◽  
R. J. Flower ◽  
J. C. Buckingham

ABSTRACT Dispersed anterior pituitary cells were used to investigate the possible roles of phospholipid metabolites released by phospholipase A2 (PLA2) in the control of immunoreactive ACTH (ir-ACTH) secretion in vitro. PLA2 (15 600–62 500 U/1), the PLA2 activator melittin (0·5–20 mg/l) and arachidonic acid (1 mmol/l) all produced increases in ir-ACTH release from the cells, whilst platelet-activating factor (PAF), prostaglandin F2α (PGF2α), the prostacyclin analogues iloprost and BW245C, the thromboxane A2 (TXA2) analogue U46619, and the leukotrienes LTB4 and LTC4 were ineffective in this respect. PGF2α (100 nmol/l and 1 μmol/l), iloprost (1 μmol/l) and BW245C (100 nmol/l and 1 μmol/l) depressed corticotrophin-releasing factor-41-induced ir-ACTH secretion, while the PAF antagonist BN52021 (10 and 100 μmol/l) and LTC4 (100 nmol/l and 1 μmol/l) had no discernable effects. The secretory responses of the cells to hypothalamic extracts (0·2 hypothalami/ml) and arachidonic acid (1 mmol/l) were generally unaffected by the cyclooxygenase inhibitors ibuprofen (10 and 100 μmol/l) and indomethacin (10 μmol/l), the TXA2 synthetase inhibitor imidazole (10 μmol/l–1 mmol/l), the lipoxygenase inhibitor nordihydroguaiaretic acid (10 and 100 μmol/l) and the dual cyclo-oxygenase/lipoxygenase inhibitors phenidone (1–100 μmol/l) and BW755C (10 and 100 μmol/l). They were, however, inhibited by the dual cyclo-oxygenase/lipoxygenase inhibitor eicosatetraynoic acid (10 and 100 μmol/l), which also blocks epoxygenase and PLA2 activity and by the cytochrome P450 inhibitor SKF-525A (1 mmol/l). The results suggest that the stimulatory effects of PLA2 and arachidonic acid on ir-ACTH secretion are not effected by products generated by the cyclo-oxygenase or lipoxygenase pathways but may be mediated by metabolites generated by the cytochrome P450 pathway. Journal of Endocrinology (1991) 130, 21–32


1988 ◽  
Vol 254 (5) ◽  
pp. E543-E548 ◽  
Author(s):  
A. J. Douglas ◽  
E. W. Clarke ◽  
D. F. Goldspink

A new technique has been developed and used to distend the uterus of nonpregnant rats for up to 5 days. Continuous distension of the saline-filled uterus induced rapid and extensive growth of the whole uterus and the myometrium by a combination of hyperplasia and hypertrophy. In both cases, 1 day after this imposition of mechanical stretch significant increases (25-50%) in the protein, RNA, and DNA contents were found, with larger changes (100-250%) being progressively expressed up to 5 days. This stretch-induced growth primarily results from a stimulation of protein synthesis (measured both in vivo and in vitro), with little or no change being evident in the rate of protein breakdown. These findings have been discussed in relation to the role of stretch in the growth of the uterus during pregnancy and stretch-induced responses found in other types of muscle.


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