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Search for other papers by J. P. MALTIER in
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SUMMARY
Injection of a monoamine oxidase (MAO) inhibitor (nialamide) into the uterus of an anaesthetized and laparotomized rat on day 20 of pregnancy severely disturbed parturition. Injection of the solvent (0·9% isotonic NaCl solution) at the same stage of gestation produced the same but less frequent disturbances. When the rats were injected on days 19 or 21, impairment was less marked than on day 20. Therefore, day 20 seems to be a critical period for the onset of parturition.
Injection of Ringer solution into the uterus on day 20 had effects analogous to those of saline injection at the same stage. Anaesthesia induced with ether, laparotomy of the pregnant rat on day 20, and handling of the uterine horns without injection of either Ringer or NaCl also disturbed parturition in 70% of the rats treated. Nevertheless, disorders were not as severe as those after injection. Laparotomy alone on day 20 did not disturb parturition.
The effects on parturition of a saline injection into the uterus on day 20 were greatly decreased when the injection was performed on pregnant rats adrenalectomized on day 14, or on pregnant rats pretreated on days 18 and 19 with an agent blocking the adrenergic β receptors (propranolol); 70–80% of the treated rats had normal deliveries.
In control rats, uterine catecholamine levels were markedly modified between days 21 and 22 of gestation. These changes did not occur in rats injected with MAO inhibitor or saline.
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SUMMARY
In control rats, the concentrations of catecholamines in the uterus were markedly modified between days 21 and 22 of gestation, just before parturition; there was a considerable decrease in the concentration of adrenaline (−73%), whereas the level of noradrenaline increased significantly.
Of rats ovariectomized on day 19, 59% underwent abnormal parturition, and the uterine concentration of catecholamines remained constant; on day 22 of gestation, the concentration of adrenaline was twice as high as that in control rats. Injections of progesterone during late pregnancy resulted in prolonged pregnancies in 100% of those rats injected. Changes in the uterine concentrations of catecholamines observed in control rats did not take place in the injected animals, and on day 22 of gestation the concentration of adrenaline was three times that in control rats. Injections of oestrogen in late pregnancy advanced littering in rats which normally produced late litters. In the uterus, a considerable decrease in the concentration of adrenaline was observed and this was similar to that observed in control rats, except that the reduction occurred earlier.
Sham treatments (sham ovariectomies or injections of solvent in which oestrogen or progesterone were administered) had no effect on the timing of parturition or the uterine concentration of catecholamines, compared with control rats.
The concentration of adrenaline in the uteri of pregnant rats was controlled by steroid hormones and it seems that a very low concentration was required for normal parturition.
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Search for other papers by V Cavailles in
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We analysed the antiproliferative activity of various histone deacetylase (HDAC) inhibitors such as trichostatin A (TSA) on human breast cancer cells. We observed a lower sensitivity to HDAC inhibition for oestrogen receptor negative (ER-) versus positive (ER+) cell lines. This differential response was associated neither with a modification of drug efflux via the multidrug resistance system nor with a global modification of histone acetyltransferase (HAT)/HDAC activities. In contrast, we demonstrated that in ER+ breast cancer cells the p21(WAF1/CIP1) gene was more sensitive to TSA regulation and was expressed at higher levels. These differences were observed both in transient transfection experiments and on the endogenous p21(WAF1/CIP1) gene. The Sp1 transcription factor, which was shown to interact in vitro with both class I and class II HDACs, is sufficient to confer the differential sensitivity to TSA and participated in the control of p21(WAF1/CIP1) basal expression. Finally, re-expression of ERalpha following adenoviral infection of ER- breast cancer cells increased both p21(WAF1/CIP1) protein accumulation and the growth inhibitory activity of TSA. Altogether, our results highlight the key role of ERalpha and p21(WAF1/CIP1) gene expression in the sensitivity of breast cancer cells to hyperacetylating agents.
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Search for other papers by F Cavaille in
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Amniotic fluid (AF) collected from ewes and goats at mid gestation displayed mitogenic activity in mouse fibroblasts. Upon fractionation of this material by size exclusion chromatography, the mitogenic activity was resolved into two peaks, whose activity was inhibited by an anti-IGF type 1 receptor blocking antibody. One of the peaks contained IGF-I and IGF-II (mature form), whereas the other contained high M(r) precursor forms of IGF-II. The presence in this latter fraction of IGF-binding proteins (IGFBP) suggests that the AF IGFBPs do not efficiently inhibit the mitogenic activity of the high M(r) forms of IGF-II. In agreement with this conclusion, exogenous IGFBP-1 failed to affect this activity. Analysis of IGF-II in sheep AF showed that the AF concentrations of both forms of IGF-II increased dramatically from mid pregnancy until 106-120 days of gestation, and fell thereafter. The amniotic IGFBPs followed a similar evolution. High M(r) forms of IGF-II were also found in human AF, with a pattern of electrophoretic migration different from that of sheep. We suggest that the precursor forms of IGF-II may play an important role in foetal development.
