Dopamine-B-hydroxylase activity in rat hypothalamus during the estrus cycle.

This experiment provides a direct test of our previous suggestion that estradiol regulates dopamine-B-hydroxylase (DBH) activity in hypothalamic loci. Anterior, medial and posterior hypothalamic slices from triplets of rats were taken during estrus and diestus and assayed for DBH activity using the technique of Molinoff et al. [15]. DBH activity was measured in hypothalamic slices on three different occasions from three triplets during the estrous phase of the cycle and also from separate triplets during the diestrous stage of the cycle. Results showed a significant increase in DBH activity during the estrous phase of the cycle. Increased activity did not appear to be anatomically localized within the tissue slices. Explanation of the results has been discussed in terms of possible mechanisms of action.     

Bupivacaine kinetic changes during the oestrous cycle in rats.

Abstract— After a single 20 mg kg^?1 i.p. dose during pro-oestrus, oestrus or dioestrus, bupivacaine kinetics in rats were not significantly different except for C_max which was significantly higher during dioestrus.     

Coordinated expression of multidrug resistance-associated proteins (Mrps) in mouse liver during toxicant-induced injury.

Following acute chemical injury, hepatocytes are generally more resistant to toxicant re-exposure. Alterations in expression of hepatobiliary transport systems may contribute to this resistance by preventing accumulation of potentially toxic chemicals. Previous data demonstrate the concomitant reduction of uptake transporter and induction of efflux transporter mRNA during chemical liver injury. The present study further characterizes the expression of multidrug resistance-associated proteins 1-4 (Mrp1-4), breast cancer resistance protein (Bcrp) and sodium-taurocholate co-transporting polypeptide (Ntcp) in mouse liver following administration of the hepatotoxicants acetaminophen (APAP) and carbon tetrachloride (CCl4). Mice received hepatotoxic doses of APAP (400 mg/kg), CCl4 (10 or 25 microl/kg), or vehicle, ip. Livers were collected at 6, 24, and 48 h for Western blot quantification and immunofluorescence analysis. Protein expression of Bcrp was unchanged with treatment. Ntcp levels were preserved in APAP-exposed livers and reduced to 30-50% of control after CCl4. Conversely, Mrp1-4 expression was differentially up-regulated. CCl4 increased Mrp1 (3.5-fold), Mrp2 (1.4-fold), and Mrp4 (26-fold) while reducing Mrp3 levels to 20% of control. Administration of APAP enhanced expression of Mrp2 (1.6-fold), Mrp3 (3.5-fold), and Mrp4 (16-fold). Immunostaining of liver sections obtained 48 h after hepatotoxicant treatment confirmed expression patterns of a subset of transporters (Bcrp, Ntcp, Mrp3, and Mrp4). Double immunofluorescence imaging demonstrated the simultaneous down-regulation of Ntcp and up-regulation of Mrp4 in hepatocytes adjacent to the central vein after CCl4. Altered expression of transporters may reduce the overall chemical burden of an injured liver during recovery and contribute to the resistance of hepatocytes to subsequent toxicant exposure.     

Fluctuations in responses to diazepam during the oestrous cycle in the mouse.

Administration of diazepam (0.28 mg/kg, IP; 60 min) to male mice or to female mice at oestrus or dioestrus increased the number of transitions made between the light and dark chambers of a test apparatus, a presumed anxiolytic action. However, the same dose of diazepam had no effect on light/dark transitions at late dioestrus, proestrus, or metoestrus II. At metoestrus I, this test dose of diazepam induced a decrease in the number of light/dark transitions and significant changes in other test parameters indicative of an increase in fearfulness or light aversion. Concentrations of diazepam in the brain after intraperitoneal injection were not influenced by the stage of the oestrous cycle, suggesting that the observed changes in responses to diazepam reflect changes in sensitivity to this drug rather than alterations in distribution or metabolism. The results indicate a physiological influence of ovarian steroid hormones on sensitivity to the benzodiazepine tranquilisers.     

Role of endothelium in the human uterine arteries during normal menstrual cycle.

1. The present experiments were designed to investigate the role of endothelium in the human uterine arteries during the normal menstrual cycle. 2. Acetylcholine (ACh) produced a concentration-dependent relaxation response during the higher level of plasma 17 beta-oestradiol (E2) (follicular and luteal phases, E2 = 131.9 +/- 15.9 pg ml-1, n = 13; group I). However, the agent did not produce a definite relaxation, but produced a slight contraction during the ovulatory and menstruation phases (E2 = 19.8 +/- 2.9 pg mg-1, n = 5; group II). During the follicular and luteal phases (E2 = 181.1 +/- 9.0 pg ml-1, n = 6), ACh produced a slight contraction, but not relaxation in 6 cases (group III). Relaxation in response to A23187 in group II was not different from that in group I, while it was significantly (P < 0.05 and P < 0.005) reduced in group III. Sodium nitroprusside (SNP)-induced relaxation was similar in the three groups. 3. Correlation between the maximum response to ACh and the plasma E2 was highly significant (gamma = 0.8142, P < 0.001) in 18 cases of groups I and II, but not in all 24 cases including group III (gamma = 0.1183, NS). 4. Relaxations in response to ACh in group I or A23187 in all groups were abolished after removal of the endothelium. In group I, ACh- and A23187-induced relaxations were greatly inhibited by methylene blue or NG-nitro-L-arginine (L-NOARG) and partially inhibited by indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)     

依托泊苷对雌激素周期小鼠阴道上皮细胞PCNA表达的影响

目的探讨依托泊苷(VP-16)对银屑病模型雌激素周期小鼠阴道上皮细胞细胞增殖核抗原(PCNA)表达的影响。方法采用雌激素周期小鼠阴道上皮模型,不同组别的小鼠给予VP-16或甲氨喋呤,观察VP-16对小鼠阴道上皮细胞有丝分裂及PCNA表达的影响。结果与正常组相比,模型组有丝分裂指数明显升高,PCNA表达显著增加,VP-16组有丝分裂指数明显下降,PCNA表达显著减少。结论VP-16可能通过抑制表皮细胞异常增殖及PCNA表达发挥治疗银屑病的作用。     

Functional changes in GABAA receptor stimulation during the oestrous cycle of the rat.

1. Slices of rat cuneate nucleus were used to study whether or not gonadal steroids influence the gamma-aminobutyric acid (GABA) system in vivo. Females in different stages of the oestrous cycle as well as steroid-treated (oestrogen, progesterone or both) ovariectomized animals were used. 2. Functional changes in the GABAA receptors were assayed using the effects of potentiators (benzodiazepine, barbiturate) and antagonists (picrotoxin) on the muscimol control dose-response curves. 3. The potentiating effect of the benzodiazepine, flurazepam was unchanged during the oestrous cycle, and the hormone treatments did not alter this effect. 4. During oestrus, an increase was seen in the potentiating effect of the barbiturate (pentobarbitone). This suggests a synergistic effect between barbiturates and gonadal steroids. Progesterone treatment also increased the effect of pentobarbitone. 5. The antagonistic action of picrotoxin was unaffected during the oestrous cycle. However, progesterone (or progesterone and oestrogen) treatment reduced the potency of picrotoxin. 6. This study supports the idea that endogenous steroids (presumably progesterone) affect the GABAA receptors during the oestrous cycle by a mechanism associated with the barbiturate site of the GABAA receptor complex.     

Rat uterine contractility and the activities of uterine adenyl cyclase and phosphodiesterase during the estrus cycle

A study has been made of the activities of rat uterus adenyl cyclase and phosphodiesterase, and the inhibitory effect of theophylline on uterine contractions at various stages of the estrus cycle. The activities of adenyl cyclase and phosphodiesterase at proestrus were found to be 2.52 ± 0.28 pmoles/min/mg of protein and 1.90 ± 0.30 nmoles/min/mg of protein, respectively. Activities of both the enzymes increased from proestrus to peak values at metestrus (early metestrus for adenyl cyclase and late metestrus for phosphodiesterase) and then fell until the following proestrus. Theophylline inhibition of oxytocin-induced maximum uterine contractions was found to be greatest at early metestrus. Similarly, the oxytocin concentration producing 40 per cent maximum contraction in the presence and absence of the theophylline

$\text{Oxytocin}\text{(E}{}_{40}\text{)+}\text{theophylline}\text{Oxytocin}\text{(E}{}_{40}\text{)}$

was also highest at early metestrus. These findings indicate that, at early metestrus, cellular turnover of cyclic AMP may be high and that the exaggerated inhibition of oxytocin- induced maximum contraction and the high value of

$\text{Oxytocin}\text{(E}{}_{40}\text{)+}\text{theophylline}\text{Oxytocin}\text{(E}{}_{40}\text{)}$

could be due to extensive accumulation of cyclic AMP produced from theophylline inhibition of phosphodiesterase.     

Association between estrus cycle-related changes in respiration and estrus cycle-related aggression in outbred female Wistar rats.

Premenstrual dysphoric disorder is characterized by irritability surfacing during the luteal phase of the menstrual cycle, and disappearing shortly after the onset of menstruation. Although the cardinal symptoms of premenstrual dysphoria are different from those of panic disorder, the two conditions share a number of traits indicating that they both may be associated with abnormalities in the regulation of respiration. Both subjects with panic disorder and subjects with premenstrual dysphoria are hence reported to display enhanced respiratory variability, and to experience anxiety when exposed to CO(2). In the present study, the possible influence of the estrus cycle on respiratory parameters in outbred female rats of the Wistar strain was investigated. Before being tested with respect to respiration, the rats were subdivided into two groups: those displaying estrus cycle-related variation in aggression, as evaluated using the resident intruder paradigm, and those not showing aggression throughout the cycle. Whereas the former group was found to display higher respiratory rate during the diestrus phase than during the proestrus/estrus phase, no cycle-related variation in respiration was observed in animals not showing cycle-related variation in aggression. The results support previous studies indicating that the estrus cycle exerts an influence on respiration, and suggest that rats prone to cycle-related aggression are more sensitive also to the influence of hormonal cyclicity on respiration. The possible bearing of these findings for the aberration in respiration displayed by subjects with premenstrual dysphoria is discussed.     

Red blood cell polyamine evolution during normal growth in mouse.

Red blood cell (RBC) polyamine levels were studied at different ages in growing mice. Contrary to RBC from adult mice, high levels of the three polyamines Putrescine, Spermidine (Spd), Spermine (Spm) were detected in erythrocytes from newborn mice. These levels progressively decreased during growth. As previously reported in experimental and clinical studies related to tumor progression or normal tissue regeneration, a statistical correlation between Spd and Spm was noticed in this study concerning normal growth. As regards this correlation, two separate periods appeared during development. The slope values of the straight regression line were calculated for these periods and showed highly significant differences.     

Features of the normal menstrual cycle.

The information currently available concerning the endocrine aspects of the human menstrual cycle from puberty to menopause is briefly summarized. Features of abnormal menstrual cycles are defined and the endocrine features of the menopausal state summarized. Cautions are expressed regarding the physiologic nature of current and contemplated replacement therapy.     

The effects of estrus cycle on drug metabolism in the rat

The effect of the female rat estral cycle on microsomal drug metabolism in-vivo and in-vitro has been studied. Two microsomal enzymes, aminopyrine-N-demethylase and aniline hydroxylase showed a greater specific activity (p less than 0.01) in the diestrus phase of the estral cycle while the oxidative enzyme aryl hydrocarbon hydroxylase and the conjugative enzyme, glucuronyl transferase, were not affected. In vivo studies which included theophylline and antipyrine metabolism, and hexobarbital sleeping times showed no difference between the different phases of the estral cycle. Conflicting evidence about the effect of steroid sex hormones on hepatic drug metabolism is discussed.     

Changes in breast volume during normal menstrual cycle and after oral contraceptives.

The volume of the left and right breasts was measured daily in four nulliparous women during normal menstrual cycles and after the use of oral contraceptives. Breast volume increased significantly in the second half of both normal and contraceptive-controlled cycles. The mean total change in volume throughout the cycle was 100 ml under natural conditions and 66 ml on oral contraceptives.     

Peripheral plasma progesterone concentration in relation to estrus expression in Sahiwal cows.

The present study investigated the changes in peripheral plasma progesterone levels in relation to expression of estrus in Sahiwal cows. Out of a total of five estrus, three were accompanied by overt signs whereas the remaining two were silent estrus. In cows with overt estrus, plasma progesterone concentrations during periestrus, early luteal, midluteal and late luteal phase were 0.40 +/- 0.02, 0.74 +/- 0.10, 1.94 +/- 0.22 and 0.63 +/- 0.16 ng/ml, respectively and the corresponding values in cows with silent estrus being 0.47 +/- 0.03, 0.94 +/- 0.08, 1.39 +/- 0.13 and 0.95 +/- 0.19 ng/ml, respectively. The overall plasma progesterone levels in cows that exhibited overt estrus was 1.23 +/- 0.99 ng/ml as against 1.08 +/- 0.09 ng/ml in silent estrus. It was concluded that progesterone levels were lower (P > 0.05) in cows that exhibited silent estrus compared to overt estrus.     

Cell cycle dynamics of maturation-promoting factor during mouse oocyte maturation

The changes in activity of a cytoplasmic maturation-promoting factor (MPF), capable of inducing resumption of meiosis when injected into starfish oocytes, were examined during mouse oocyte maturation. MPF appeared first at the time of germinal vesicle breakdown (GVBD), and its activity fluctuated along with the meiotic cycle: it reached a peak at the first metaphase and disappeared at the first polar body emission. Then MPF reappeared and reached a peak again at the second metaphase. Thus, a good correlation was found between MPF activity and meiotic metaphase. When mouse oocytes were treated with cytochalasin D, metaphase chromosomes and meiotic spindles were maintained after the first metaphase. In such a case, MPF activity remained at an elevated level after the first peak. Addition of cycloheximide to these cytochalasin-treated oocytes caused diminution of MPF activity, followed by chromosome movement, decondensation and formation of nucleus-like structures. Thus, it is likely that disappearance of MPF activity induces transition from metaphase to the subsequent processes. Further, detailed observation of chromosomes revealed that only the monovalent chromosomes were competent to decondense in response to the disappearance of MPF. Therefore, it was suggested that dissociation of synapsis is necessary for the decondensation of chromosomes.     

抑抗汤对胚泡着床障碍小鼠子宫白血病抑制因子表达的影响

目的 观察抑抗汤对小鼠胚泡着床障碍的影响.方法 将妊娠小鼠随机分为正常组、模型组、中药组和对照组.中药组按照抑抗汤灌胃剂量进一步分为低、中、高剂量组,分别每日以0.4、0.6、0.8 ml抑抗汤灌胃;对照组每日0.8ml生理盐水灌胃.模型组和中药组于第4天晨皮下注射0.8 g/L米非司酮溶液0.1ml.第5天观察各组小鼠妊娠率和平均胚泡着床数,ELISA法检测小鼠宫腔冲洗液白血病抑制因子(LIF)蛋白浓度,实时荧光定量PCR检测子宫内膜LIF表达水平.结果 模型组妊娠率和平均胚泡着床数较正常组明显下降(P＜0.01).中药组妊娠率和平均着床胚泡数均较模型组呈剂量依赖性增加(P＜0.05).中药组LIF蛋白和mRNA水平较模型组升高.结论 抑抗汤可能通过促进LIF表达促进胚泡着床.