Constitutive Secretion of Interleukin-6 by Human Decidual Stromal Cells in Culture. Regulatory Effect of Progesterone

PROBLEM : Although several studies have demonstrated that decidual stromal cells (DSC) can secrete cytokines in culture, none of these studies documented the purity of the cultures. Since other cells of the decidua, such as macrophages and epithelial cells, also produce cytokines, it is important to ensure purity of the culture so that cytokine production can be ascribed with confidence to DSC. METHOD : DSC from early human pregnancies were highly purified and maintained in culture. Basal secretion by these cells of IL-6, together with other cytokines considered critical for pregnancy (IL-1β, TNFα and IFNγ), was measured with immunological techniques. RESULTS : We found that DSC in culture produce insignificant quantities of IL-1β, TNFá and IFNΓ, but appreciable amounts of IL-6. The production of this later cytokine was, however, inhibited by the effect of progesterone. CONCLUSIONS : Basal production of IL-6 by DSC may be involved in physiological functions at the maternal-fetal interface. Nevertheless, the secretion of this cytokine is regulated by progesterone, probably to prevent excessive production of this cytokine from triggering an inflammatory response that might compromise pregnancy.     

Tumor nuclear grade,estrogen receptor,and progesterone receptor: Their value alone or in combination as indicators of outcome following adjuvant therapy for breast cancer

Summary Previous reports by us have shown that the outcome of breast cancer patients who have received systemic adjuvant therapy is influenced by tumor estrogen or progesterone receptor (ER or PR) content or by nuclear grade. This publication provides information regarding the relative merit of those three markers. Findings from patients receiving L-PAM plus 5-FU (PF) or PF plus tamoxifen (PFT) indicate that the disease-free survival and survival within each regimen was almost identical when related to either ER, PR, or nuclear grade. Those having tumors with either of the receptors 10 fmol or a good nuclear grade had a better outcome through five postoperative years than did those with ER or PR 0–9 fmol or poor nuclear grade. The magnitude of the difference was similar for each of the three discriminants. Since they were found to be of equal predictive value, one marker might well serve as a substitute for another. Cox regression analyses, however, clearly indicate that ER, PR, and nuclear grade have an independent influence on outcome and that a more accurate assessment of outcome is obtained when more than one marker is employed. Thus, information should be obtained on as many markers as possible. This conclusion is supported by observations presented which indicate that nuclear grade in combination with either or both of the receptors is a better predictor than either marker alone and that, as indicated by life table probability values and relative odds ratios, an increasing number of favorable tumor prognostic indicators results in a better patient outcome particularly in PFT-treated patients. A possible explanation is considered for why the separation of receptor/nuclear grade categories is more orderly and pronounced in PF-treated patients receiving tamoxifen than in those given PF alone. See Appendix I     

雌孕激素序贯用药治疗流产术后宫腔残留患者的临床价值分析

目的分析雌孕激素序贯用药治疗流产术后宫腔残留患者的临床价值。方法选取2017年1月至2019年12月我站收治的人工流产患者60例,按治疗方式不同分为对照组(28例)和观察组(32例)。对照组采用刮宫治疗,观察组于人工流产术后第7 d行B超检查,观察宫腔残留情况后采用药物治疗。比较两组的临床疗效、并发症。结果两组的总有效率比较无统计学差异(P>0.05)。观察组的腹痛发生率低于对照组,出血时间短于对照组(P <0.05)。结论雌孕激素序贯用药治疗能够有效清除宫腔残留,缩短出血时间,减轻腹痛,有利于重新建立正常的月经周期,促进子宫功能修复,避免再次刮宫对子宫内膜的损伤及手术对患者造成的不良身心应激,具有较高的临床推广价值。     

干扰素－α对兔离体的卵巢颗粒细胞孕酮生成的影响

本研究应用离体培养的兔卵巢颗粒细胞观察了ＩＦＮ－ａ对孕酮生成的影响。细胞预培养２４ｈ后，用ＩＦＮ－ａ（５０～８００Ｕ／ｍｌ）处理培养的颗粒细胞１２ｂ刺激孕酮的生成并呈剂量依赖关系。在ＩＦＮ－ａ加入培养细胞后３、１２和２４ｈ．刺激作用非常明显，但刺激作用的幅度在３和１２ｈ较大，分别为对照组的２４和２０倍。此外，ＩＦＮ－ａ刺激离体兔颗粒细胞孕酮生成的作用被同时加钙螫合剂ＥＧＴＡ（１ｍｍｏｌ／Ｌ）或钙通道阻断剂异搏定（ｖｅｒ）２０和２００μｍｏｌ／Ｌ所抑制。本研究结果表明，ＩＦＮ－ａ刺激离体兔卵巢颗粒细胞孕酮的生成，其作用依赖于细胞外的Ｃａ２＋浓度。     

Variant progesterone receptor mRNAs are co-expressed with the wild-type progesterone receptor mRNA in human endometrium during all phases of the menstrual cycle

Progesterone receptor (PR) variant mRNAs in human endometrium could encode proteins with the potential to alter progesterone action in states of normal and abnormal endometrial development. We have assessed the expression levels of mRNA for the wild-type PR and splice variants of PR mRNA lacking exon 4 (del-4 PR), exon 6 (del-6 PR), exons 4 and 6 (del-4&6 PR), and part of exon 4 (del-p4 PR) or part of exon 6 (del-p6 PR) in the human endometrium throughout menstrual cycle development. Eighty-eight endometrial specimens (47 proliferative, 41 secretory) were collected from patients undergoing hysterectomy for benign gynaecologic causes. Measurements by RT-PCR indicated that mRNAs for wild-type PR, and splice variants del-4 PR, del-6 PR, del-4&6 PR, del-p6 PR, and a novel del-p4 PR were detected in all endometrial specimens throughout the menstrual cycle. Higher levels of wild-type PR and all PR variant mRNAs were found in the early and mid-proliferative endometrial phases than in secretory endometrium. The relative expression of mRNA for all PR variants compared to wild-type PR mRNA, however, did not change through all stages of endometrial development. We, therefore, found no evidence of differential co-expression of the PR variants compared with wild-type PR during normal menstrual development. Future studies will determine if the expression profile of PR variant mRNAs will be different in the endometrium of patients with infertility, recurrent pregnancy loss, or endometrial adenocarcinoma.     

Study on Relevance of Endothelin to Abnormal Uterine Bleeding Associated with Long-Term Subdermal Implants Use

Objective To investigate the relationship between estradiol, progesterone and endothelin (ET) and abnormal uterine bleeding after using sub-dermal contraceptive implant Materials & methods A prospective self-control clinical trial was conducted in 29 women in the self-control group. Blood samples were obtained on four occasions across the different phases of menstrual cycle before and after using implant. A blood sample was taken for a single determination in another 59 women in the already-use implant group. Plasma of estradiol, progesterone and endothelin were determined by using radioimmunoassays (RIA) in both groups.Results The level of estradiol and progesterone had no significant differences in women before and after using implant in self-control group. The level of estradiol,progesterone had no differences between women with normal and abnormal menstrual cycle in both groups. The levels of plasma endothelin (ET) in women with abnormal bleeding pattern were higher than women with normal bleeding pattern, but difference was not significant. Women with abnormal bleeding pattern had significantly higher ET level than that in women with normal bleeding pattern before using implants,especially in early-proliferative phase and mid-proliferative phase. the level of plasma endothelin was significantly higher in women with disturbed bleeding pattern than that in normal women in the already-use group.Conclusion High serum concentrations of ET are likely to be correlated with abnormal uterine bleeding in long-term subdermal contraceptive implants users.     

米非司酮对大鼠黄体和子宫内膜纤溶酶原激活因子的调节作用

采用纤维蛋白铺盖和放射免疫方法研究了米非司酮(RU486)对培养颗粒细胞及黄体细胞纤溶酶原激活因子(包括组织型tPA和尿激酶型uPA)的作用。结果示RU486能明显拮抗入绒毛膜促性腺激素(hCG)促进颗粒细胞tPA活性及孕酮分泌的作用。RU486和PGF2α能明显促进黄体细胞tPA分泌,但孕酮产生明显被抑制。用组织学培养的方法,结果表明,RU486能刺激妊娠子宫内膜tPA和uPA分泌。这些结果表明RU486的抗生育作用部分能通过PA起到抗排卵、溶黄体及抗早孕的作用。     

The relationship of urinary and plasma androgens to steroid receptors and menopausal status in breast cancer patients and their influence on survial

Summary The relationships between urinary 11-desoxy-17-oxo steroids (11-DOS), the ratio of 11-DOS to urinary 17-hydroxycorticosteroids (urinary discriminant ratio), plasma levels of the adrenal androgens dehydroepiandrosterone (DHA), DHA sulphate (DHAS), and 7-hydroxy DHA (7DHA), and tumour oestrogen receptor (ER) and progesterone receptor (PR) status were examined in pre, peri-, and postmenopausal women with breast cancer. Androgenic steroids and their metabolites decreased with age in women with breast cancer. In perimenopausal women there was a significant association of PR positive tumours and high androgen levels, whereas in postmenopausal women high androgen levels were associated with ER negative tumours. Survival was significantly related to plasma DHA level and tumour steroid receptor status. Thus, adrenal androgen levels below the group mean were associated with significantly decreased survival in women with postmenopausal receptor-positive tumours, and the association was particularly apparent in those who were axillary node negative. Since the number of patients studied was small these results should be regarded as provisional in nature. Nonetheless, the identification of this subgroup of node negative breast cancer women with reduced survival may be important when considering node negative patients for adjuvant therapy.     

Immunohistochemical localization of receptors for progesterone and oestradiol-17 beta in the implantation site of the rhesus monkey

The aim of the present study was to examine the cellular basis of the involvement of oestradiol and progesterone in blastocyst implantation in the primate. To this end, the cellular distribution of receptors for oestradiol (ER) and progesterone (PR) in fetal trophoblast cells and in endometrial compartments of timed lacunar (pre-villous) and villous stages of placentation in primary implantation sites collected on days 13-22 of gestation were investigated in rhesus monkeys. Both in pre-villous stage tissue and in villous stage tissue, cytotrophoblast cells and syncytiotrophoblast cells and other trophoblast derived cells were PR positive, while they were generally ER negative. Maternal endometrial cells were ER negative, while epithelial cells, stromal cells and vascular endothelial cells in maternal endometrium showed heterogeneous staining patterns for PR depending on their relative location; these patterns, however, correlated well with glandular hyperplasia and differentiation, stromal-decidual transformation and vascular response seen during blastocyst implantation.     

自然排卵与注射人绒毛膜促性腺激素促排卵时阴道脱落细胞雌、孕激素受体的研究

目的：研究排卵期阴道脱落细胞的雌、孕激素受体。方法：自然排卵妇女、注射人绒毛膜促性腺激素（ｈｕｍａｎ ｃｈｏｒｉｏｎｉｃ ｇｏｎａｄｏｔｒｏｐｉｎ,ｈＣＧ）促排卵妇女排卵期阴道脱落细胞,应用免疫组织化学ＡＢＣ 法和图像分析技术进行雌激素受体（ｅｓｔｒｏｇｅｎｒｅｃｅｐｔｏｒ,ＥＲ） 和孕激素受体（ｐｒｏｇｅｓｔｅｒｏｎｅｒｅｃｅｐｔｏｒ,ＰＲ）的定位和定量研究。结果：两组组内排卵前、后阴道脱落细胞ＥＲ比较均无差异;注射ｈＣＧ 后阴道脱落细胞的ＥＲ在排卵前和排卵后均较自然排卵组有明显增高;自然排卵组ＰＲ在排卵后较之排卵前明显升高。结论：排卵前后阴道上皮细胞ＥＲ 无明显变化;ｈＣＧ可提高阴道上皮细胞ＥＲ 水平;排卵后阴道上皮细胞ＰＲ增加。