Effect of ovarian steroids on basal and oxytocin-induced prostaglandin F2alpha secretion from pig endometrial cells

These studies were undertaken to determine how treatment with 100 nM progesterone and/or 10 nM oestradiol-17beta acutely (3 h; Experiment 1) or chronically (72 h; Experiments 2-4) influenced basal and oxytocin (OT)-stimulated prostaglandin (PG) F(2alpha) secretion, in enriched cultures of pig endometrial luminal epithelial, glandular epithelial and stromal cells obtained on Day 16 (Experiments 1, 2 and 4) or Day 12 (Experiment 3) after oestrus. In Experiment 1, acute treatment with progesterone stimulated PGF(2alpha) secretion from each cell type on Day 16, whereas acute oestradiol treatment inhibited the stimulatory action of progesterone on PGF(2alpha) secretion only in glandular epithelial cells. In Experiment 2, OT stimulated phospholipase (PL) C activity in luminal epithelial cells on Day 16 only in the presence of chronic oestradiol treatment. For glandular epithelial cells on Day 16, OT stimulated PLC activity only in the presence of chronic treatment with steroid. In stromal cells on Day 16, OT stimulated PLC activity in the absence of steroids and the response to OT was further enhanced by oestradiol. In the absence of chronic treatment with steroid, OT did not stimulate PGF(2alpha) secretion from luminal epithelial cells, but oestradiol induced a response to OT. For glandular epithelial cells, OT-induced PGF(2alpha) secretion was not altered by steroids, whereas the stimulatory response to OT was inhibited by oestradiol or progesterone in stromal cells. For endometrial cells obtained on Day 12 after oestrus in Experiment 3, OT only stimulated PGF(2alpha) release from glandular epithelial and stromal cells. For luminal epithelial cells obtained on Day 16 after oestrus and cultured under polarizing conditions in Experiment 4, secretion of PGF(2alpha) occurred preferentially from the basolateral surface and was stimulated by OT more from the basolateral surface than from the apical surface. Oxytocin-induced PGF(2alpha) secretion from the apical surface was enhanced by chronic treatment with oestradiol, whereas that from the basolateral surface was enhanced by chronic treatment with progesterone. In summary, oestradiol enhanced OT-induced PGF(2alpha) secretion from the apical surface of luminal epithelial cells and reduced the response of stromal cells to OT, actions that may contribute to the reorientation of PGF(2alpha) from endocrine secretion (i.e. towards the uterine vasculature) to exocrine secretion (i.e. towards the uterine lumen) during pregnancy recognition in pigs.     

Control of endometrial phosphoinositide hydrolysis and prostaglandin F2alpha secretion in pigs

This study examined the control of endometrial phosphoinositide (PI) hydrolysis and prostaglandin (PG) F2alpha release by oxytocin (OT) and vasopressin in cyclic pigs on Day 15 post oestrus. In Expt 1, OT and arginine-vasopressin (AVP) increased endometrial PI hydrolysis (P<0.01), but only OT stimulated (P<0.01) PGF2alpha secretion. In Expt 2, OT and lysine-vasopressin (LVP) increased PI hydrolysis (P<0.01). No difference was detected between the 100 nM and 200 nM concentrations of OT or between the 100 nM and 200 nM concentrations of LVP. The increase in PI hydrolysis was greater (P<0.05) for 100 nM OT plus 100 nM LVP than for the 100 or 200 nM concentrations of OT or LVP alone. In Expt 3, OT (P<0.01) and LVP increased (P<0.01) PI hydrolysis. An OT antagonist abolished (P<0.01) the OT-induced increase in PI hydrolysis, but did not significantly alter the LVP-induced increase. A type 2 VP antagonist completely inhibited (P<0.01) the LVP-induced increase in PI hydrolysis, but only partially antagonized the stimulatory effect of OT (P<0.01). These results are consistent with the proposal that OT acts through specific receptors to promote endometrial PGF2alpha secretion in pigs.     

Serum prostaglandin F2alpha levels and contraceptive techniques

Prostaglandin F_2α (PGF_2α) concentrations were determined in the serum of women using either no contraception or barrier methods, an intrauterine contraceptive device (IUCD) or oral contraceptives. Samples were taken between days 1–5 and days 18–23 of the menstrual cycle, when levels of sex steroids are low and then high. PGF_2α levels were not significantly different between the groups at the times studied, although those using oral contraceptives had significantly higher levels when on tablets.     

Chronoperiodicity in response to the intra-amniotic injection of prostaglandin F2alpha.

The chronoperiodicity in response to a single intra-amniotic injection of 40 mg prostaglandin F₂α. for the induction of a mid-trimester abortion in 73 patients has been studied. The induction-abortion interval was significantly shorter when the initial intra-amniotic injection was given between 12.00 and 14.00 hours, than when it was given at other times of day. This possible chronoperiodicity is different from that previously reported. The reasons for this are unknown at present.     

Randomized trial of intracervical prostaglandin E2 gel and intraamniotic prostaglandin F2 alpha for induction of second trimester abortion

For the purpose of reducing the side effects and complication rate when inducing second trimester abortion, intracervically administered PGE2 gel was tested for the first time and compared with a single intraamniotic instillation of PGF2 alpha by a randomized allocation of 41 consecutive patients in the 13th to 24th week of gestation. In both groups the treatment was supplemented with oxytocin 5 - 6 hours after starting the induction. The methods proved of equal value as regards the abortion success rate and the induction-abortion interval, whereas the incidence of gastrointestinal side effects on intracervical application of PGE2 gel was only half as high and the occurrence of diarrhea significantly lower (p less than 0.05) with this non-invasive method than with intraamniotic PGF2 alpha. Intracervical PGE2 gel also possessed other advantages, being int. al. more acceptable by the patients and technically easier to administer.     

Prostaglandins in dysfunctional labour; evidence for altered production of prostaglandin F2 alpha

Dysfunctional labour was studied in relation to prostaglandin concentrations in amniotic fluid and production by fetal membranes. Initial clinical validation of the model established the presence of hypokinetic labour with no evidence of obstruction to the fetal progress. Prostaglandin F2 alpha (PGF2 alpha) and 13, 14 dihydro-15-keto-prostaglandin-F2 alpha concentrations in the amniotic fluid were low despite relatively normal concentrations of prostaglandin E2. Membranes removed from patients with the condition released very low concentrations of PGF2 alpha from the amniotic side with no alteration on the choriodecidual side of the membrane. Studies of free and phospholipid-associated arachidonic acid indicated normal release of arachidonic acid in dysfunctional labour. No changes in amniotic fluid-related inhibitors and stimulators of prostaglandin synthetase were detected. It is suggested that PGF2 alpha production is impaired in dysfunctional labour and that this prostaglandin is primarily involved in the progress of labour.     

Dietary (n-3) fatty acids reduce plasma F2-isoprostanes but not prostaglandin F2alpha in healthy humans

(n-3) Fatty acids are unsaturated and are therefore easily subject to oxidization; however, they have several beneficial health effects, which include protection against cardiovascular diseases. The aim of this study was to investigate whether (n-3) fatty acids, with a controlled fat quality in the background diet, affect nonenzymatic and enzymatic lipid peroxidation and antioxidant status in humans. A total of 162 men and women in a multicenter study (The KANWU study) were randomly assigned to a diet containing a high proportion of saturated fatty acids or monounsaturated fatty acids (MUFA) for 3 mo. Within each diet group, there was a second random assignment to supplementation with fish-oil capsules [3.6 g (n-3) fatty acids/d] or placebo. Biomarkers of nonenzymatic and enzymatic lipid peroxidation in vivo were determined by measuring 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) and prostaglandin F(2alpha) (PGF(2alpha)) concentrations in plasma at baseline and after 3 mo. Antioxidant status was determined by measuring plasma antioxidant capacity with an enhanced chemiluminescence assay. The plasma 8-iso-PGF(2alpha) concentration was significantly decreased after 3 mo of supplementation with (n-3) fatty acids (P = 0.015), whereas the PGF(2alpha) concentration was not affected. The antioxidant status was not affected by supplementation of (n-3) fatty acids, but was improved by the background diet with a high proportion of MUFA. We conclude that supplementation with (n-3) fatty acids decreases nonenzymatic free radical-catalyzed isoprostane formation, but does not affect cyclooxygenase-mediated prostaglandin formation.     

Induction of abortion by a single intra-amniotic injection of 40 mg prostaglandin F2alpha

The optimum dose and route of administration of prostaglandins used for the induction of middle trimester abortions has not yet been determined. Sixty-one patients had mid-trimester abortions induced by the intra-amniotic injection of 40 mg prostaglandin F_2α; 88.5% of these being successful. The injection-abortion interval for this group was 15.2 ± 8.6 hours. Parity had no effect on the success rate but the injection-abortion interval was significantly shorter in multiparous patients. Most of the abortions were incomplete. The incidence of side effects was acceptable. Only 7 patients required a second injection. This method is safe and effective in terminating mid-trimester pregnancies.     

Therapeutic abortion of early human gestation with intramuscular 15-methyl prostaglandin F2 alpha.

Plasma levels of medroxyprogesterone acetate (MPA) were determined by radioimmunoassay in five women after oral administration of 10 mg of MPA and during treatment with intravaginal rings homogenously impregnated with 100 mg of MPA. Peak plasma levels of MPA of 1.15–5.15 ng/ml were reached within two hours after oral administration. The levels thereafter rapidly declined being 0.09–0.35 ng/ml at twelve hours. During IVR treatment rather stable plasma levels between 0.37 and 0.63 ng/ml were reached. Vaginal absorption of MPA was found to be very rapid with plasma levels between 0.29 and 0.47 ng/ml already three hours after insertion of the IVR. The plasma levels found are lower than previously reported probably due to methodological differences. The plasma levels of MPA are much lower than the d-norgestrel levels found after administration of smaller amounts of d-norgestrel. This is probably explained by differences in compartmentalization of the drugs. The elimination halflife of MPA was found to be about 30 hours which is longer than for d-norgestrel (20 hours).     

Oxytocin-stimulated phosphoinositide hydrolysis and prostaglandin F2alpha secretion by luminal epithelial, glandular epithelial and stromal cells from pig endometrium. II. Responses of cyclic, pregnant and pseudopregnant pigs on days 12 and 16 post oestrus

In pigs, the exact mechanism for the shift in endometrial PGF2alpha secretion from an endocrine to an exocrine mode during pregnancy recognition is not known. The objective of this study was to examine whether this shift involved a change in the responsiveness of luminal epithelial, glandular epithelial and stromal cells to 0 or 100 nM oxytocin. Luminal epithelial cells, glandular epithelial cells and stromal cells were isolated from cyclic, pregnant or oestrogen-induced pseudopregnant gilts on Day 12 (Experiment 1) or Day 16 (Experiment 2) post oestrus (oestrus = Day 0). For cells obtained on Day 12, oxytocin stimulated PGF2alpha secretion by stromal cells (P<0.01) similarly for each reproductive status, whereas oxytocin stimulated PGF2alpha secretion from luminal and glandular epithelial cells (P<0.05) from pregnant and pseudopregnant gilts but not from cyclic gilts. For both concentrations of oxytocin, mean PGF2alpha secretion was less (P<0.05) from stromal cells of pregnant than cyclic gilts. For cells obtained on Day 16, oxytocin stimulated PGF2alpha release from stromal cells of cyclic gilts but not from stromal cells of pregnant gilts. Mean PGF2alpha secretion also was less (P<0.05) from stromal cells of pregnant gilts than cyclic gilts. Oxytocin tended to stimulate PGF2alpha release (P<0.07) from glandular epithelial cells of cyclic but not pregnant or pseudopregnant gilts. Luminal epithelial cells from all reproductive statuses were similarly unresponsive to oxytocin. In conclusion, the increased PGF2alpha secretory response to oxytocin of luminal and glandular epithelial cells from pregnant gilts on Day 12, combined with the decreased response of stromal cells from pregnant gilts on Days 12 and 16, may contribute, in part, to the shift in endometrial PGF2alpha secretion from an endocrine to an exocrine direction during early pregnancy in pigs.     

Induction of abortion by intrauterine administration of prostaglandin F2 alpha and histopathological studies of gestational sac

124 patients were selected for termination of pregnancy by (PGF) prostaglandin F2alpha administration. PG was administered by the extraamniotic route in 81 patients, whose length of gestation ranged from 8-16 weeks. PG was administered intraamniotically in 43 patients whose length of gestation ranged from 14-20 weeks. In the extraamniotic group, abortion occurred in 89% of the cases within 36 hours with a mean induction-abortion interval of 18 hours. In the intraamniotic group, abortion occurred in 86% of the cases within 48 hours with a mean induction-abortion interval of 20 hours. Histopathological studies on gestational sacs were performed in 3 groups of patients: in group 1 abortions were induced by PGF2alpha administered extraamniotically; in group 2 abortions were induced by PGF2alpha administered intraamniotically; and in group 3 specimens were obtained by hysterotomy. Edema of villi was more often observed in group 1 and increased vascularization in group 2.     

Intrauterine administration of prostaglandin F2alpha as an outpatient procedure for termination of early pregnancy

A group of 20 pregnant women requesting therapeutic abortion received a single transcervical intrauterine instillation of 5 mg prostaglandin F2alpha in 5 ml of saline between 38 and 46 days after the onset of their last menses. Of the 20 women, 13 (65%) had a successful termination of pregnancy, while the other 7 patients did not abort. A total of 7 patients, 2 of whom aborted, had severe adverse reactions, including fever, hemorrhage and hypertension. 3 of the 5 women who did not abort developed septic incomplete abortions. The low incidence of success and high incidence of complications noted in the study indicate that this method should not be utilized to terminate early pregnancy.     

Vitamin E supplementation decreases basal levels of F(2)-isoprostanes and prostaglandin f(2alpha) in rats

Lipid peroxidation is thought to be an important factor in the pathophysiology of a number of diseases and in the process of aging. We investigated the effects of supplementation with vitamin E on lipid peroxidation in rats. Both free radical-induced nonenzymatic- and cyclooxygenase-catalyzed enzymatic lipid peroxidation were investigated by measuring the levels of F(2)-isoprostanes (8-iso-PGF(2alpha)) and PGF(2alpha)-metabolite (15-K-DH-PGF(2alpha)), respectively, in blood, urine and liver. Samples were collected from control rats (n = 6) and from rats supplemented with vitamin E in the diet for 3 wk (n = 8, 20 g/kg diet of DL-alpha-tocopherol hydrogen succinate). Plasma alpha-tocopherol concentration and antioxidative capacity were greater in the vitamin E-supplemented rats than in the control rats (17.9 +/- 1.7 vs. 50.4 +/- 10.4 micromol/L, P < 0.001 and 181 +/- 6 vs. 275 +/- 27 micromol/L trolox equivalents, P < 0.001). Urine 8-iso-PGF(2alpha) tended to be lower in the vitamin E-supplemented rats (0.72 +/- 0.40 vs. 0.34 +/- 0.19 nmol/mmol creatinine, P = 0.056). Urine 15-K-DH-PGF(2alpha) was lower due to vitamin E supplementation (0.97 +/- 0.38 vs. 0.56 +/- 0. 21 nmol/mmol creatinine, P < 0.05), as was liver-free 8-iso-PGF(2alpha) concentration (0.47 +/- 0.11 vs. 0.18 +/- 0.04 nmol/g, P < 0.001). Supplementation with vitamin E did not affect plasma 8-iso-PGF(2alpha) or 15-K-DH-PGF(2alpha) concentrations, liver total 8-iso-PGF(2alpha) or plasma malondialdehyde levels. Thus, vitamin E supplementation reduced urine basal levels of biomarkers of both nonenzymatic and enzymatic lipid peroxidation. In liver, vitamin E reduced the basal level of free 8-iso-PGF(2alpha) but not total 8-iso-PGF(2alpha).     

持续皮下胰岛素输注治疗妊娠期糖尿病的效果观察

目的 分析持续皮下胰岛素输注对妊娠期糖尿病(GDM)患者血糖水平及妊娠结局的影响.方法 以2018年8月—2019年8月本院收治的GDM患者120例为研究对象,采用随机数字表法将其分为对照组和治疗组,各60例,对照组给予常规胰岛素皮下注射治疗,治疗组给予持续皮下胰岛素输注.比较两组患者治疗前后空腹血糖(FBG)、糖化血...     

On the mechanism of prostaglandin F2alpha-induced abortion in hamsters

The mechanisms by which prostaglandins (PGs) induce abortion in hamsters remain poorly understood. PGs may effect one or more of these factors: a) corpus luteum (CL) structure and/or function; b) ovarian blood supply; c) pituitary function; and d) uterine motility. A minimum s.c. dose of 12.5 μg of PGF_2α is required to abort hamsters on day 5 of pregnancy. Radioimmunoassays revealed a drop of 71% in serum progesterone (P) levels 3 hours after dosing. Pregnancy was maintained indefinitely in hamsters receiving PGF_2α on day 5 by injections of progesterone on days 4, 5, and 6. In a related experiment, pregnancy was maintained with 5 mg doses of 17α-ethyl-19-nortestosterone (ENT) before and after PGF_2α injection, thereby permitting assessment of endogenous P levels (ENT does not cross-react with antiprogesterone antisera). Serum P levels were depressed by PGF_2α in both ENT and control hamsters. Finally, PGF_2α was injected on day 6 in hypophysectomized hamsters in which pregnancy was maintained with ovine prolactin (1 mg) and ovine FSH (5 μg). Serum P levels were decreased 70% 3 hours post-injection, although pregnancy was maintained in 37% of the animals. PGF_2α thus interferes directly with P secretion by the ovary in the absence of the pituitary and in the presence of injected luteotrophic complex. A sustained drop of 85–90% in serum P levels appears to be required for PGF_2α to induce abortion in 100% of the hamsters. We conclude that PGF_2α does not permanently damage CL when pregnancy is maintained by exogenous hormones, and the involution observed by others is most likely a consequence rather than a cause of pregnancy loss.     

胰岛素泵治疗2型糖尿病高血糖状态的疗效分析

目的总结并分析采用连续皮下胰岛素输注方法强化治疗2型糖尿病高血糖状态的疗效以及剂量。方法216例血糖控制差的住院2型糖尿病患者,给予胰岛素泵强化治疗,疗程8d,不合用其他口服降糖药,观察达到满意血糖控制（FPG〈7mmol／L,2hPG〈10mmol／L）的天数以及胰岛素泵的基础量和餐前大剂量,并分析与上述指标相关的因素。结果血糖达满意控制的平均天数为（5．4±1．8）d,日基础量为（0．23±0．07）U／kg,早餐前大剂量为（0．12±0．05）U／kg,午餐前大剂量为（0．14±0．06）U／kg,晚餐前大剂量为（0．14±0．06）U／kg,在血糖满意控制后,胰岛素用量显著减少。发生低血糖症（0．04±0．21）次／人,生化低血糖（0．07±0．25）次／人,低血糖反应（0．96±1．18）次／人。结论经过胰岛素泵的强化治疗,T2DM的高血糖状态可在5—6d得以纠正。经多元回归分析,影响达目标血糖时间的因素为FPG和年龄,影响胰岛素用量的因素为糖尿病的病程、治疗前FPG和2hPG。