子宫内膜异位症孕酮抵抗机制研究进展

子宫内膜异位症（EMs）中异位内膜周期性出血形成的病灶导致女性严重的盆腔疼痛与不孕.EMs是一种雌二醇（E2）依赖性疾病,孕酮是拮抗E2的经典药物.EMs患者血清孕酮水平正常,但子宫内膜对孕酮的反应性却明显下降,导致着床期子宫内膜容受性下降,不孕症发生率增加.在临床治疗中,多数EMs患者对孕酮治疗呈现低反应或无反应,这些都称为EMs的孕酮抵抗现象.孕酮抵抗机制涉及孕酮受体（PR）的缺陷,PR辅激活子的改变,基因和环境因素的变化以及雌激素受体亚型的改变等.综述有关EMs孕酮抵抗的相关机制,为克服EMs孕酮抵抗提供理论基础.     

黄体酮对新生儿缺氧缺血性脑病作用的研究进展

新生儿缺氧缺血性脑病病死率和致残率较高,且缺乏有效的治疗方法,所以至今仍为医学界的难题.黄体酮作为神经类固醇激素已经证实对新生儿缺氧缺血性脑病有保护作用,且已经应用于Ⅱ期临床试验.该文综述黄体酮对新生儿缺氧缺血性脑病的治疗进展.     

以孕酮水平确定冻融胚胎移植时间的临床研究

目的比较基于排卵监测的方案(MOR)与基于孕酮水平监测的方案(MPR)确定自然周期冻融胚胎移植(FET)时机的临床结局。方法回顾性分析190个自然周期FET的临床资料。结果 61.1%(116/190)的周期应用MPR方案,38.9%(74/190)为MOR方案;MOR组生化妊娠率为9.5%,同MPR组(1.7%)相比显著升高(P=0.014);然而,MPR、MOR组的临床妊娠率相似,分别为53.4%及51.4%,种植率、持续妊娠率及活产率的差异亦无统计学意义(P0.05)。多元Logistic回归分析显示移植方案是生化妊娠的独立影响因素,MPR与生化妊娠呈负相关[(OR0.050,95%CI(0.004,0.593)](P=0.018)。结论在基本情况及周期治疗情况相似的患者中,与MOR方案相比,MPR方案进行自然周期FET可能获得更低的生化妊娠率(即更低的妊娠丢失率),但仍需进一步研究证实。     

Progestin-inducible EDD E3 ubiquitin ligase binds to α4 phosphoprotein to regulate ubiquitination and degradation of protein phosphatase PP2Ac

Mammalian α4 phosphoprotein binds to the protein phosphatase 2A catalytic subunit (PP2Ac) to regulate PP2A activity, and to poly(A)-binding protein (PABP) and progestin-inducible EDD E3 ubiquitin ligase. This study showed induction of the EDD protein by progesterone, 17β-estradiol and prolactin in breast cancer cells. Co-immunoprecipitation analyses, using lysates of COS-1 cells transfected with α4-deletion constructs, showed the α4 N-terminus binding to endogenous PP2Ac and PABP, and the C-terminus to EDD. Monoubiquitinated α4 in MCF-7 cells was unaffected by EDD-targeting siRNA (siEDD) nor by non-targetting siNT, thus, EDD does not ubiquitinate α4. PP2Ac is polyubiquitinated, and 36-kDa PP2Ac only was detected in siEDD- or siNT-transfected cells. However, treatment with proteasomal inhibitor MG132 showed polyubiquitinated-PP2Ac molecules (∼65–250 kDa) abundantly in siNT controls but low in siEDD-transfectants, implicating PP2Ac as an EDD substrate. Finally, progesterone induction of EDD in MCF-7 cells correlated with decreased PP2Ac levels, further implicating hormone-inducible EDD in PP2Ac turnover.     

Progesterone use in assisted reproductive technology

Progesterone is the main hormone in the luteal phase. It plays a key role in preparing the uterus for a possible pregnancy, and in maintaining it after it has occurred. In assisted reproduction treatments, there is usually a luteal phase deficiency, so it is necessary to supplement this critical phase to obtain the best results, not only of implantation but also of ongoing pregnancy. Among all the available options, exogenously administered progestogens are the most used, as they have proven their efficacy and safety. This review will address the most relevant aspects of luteal phase support with progesterone in the different scenarios an embryo transfer can be performed, such as the stimulated cycle, the artificial cycle, or the natural cycle. Although there is no evidence of the perfect protocol for all patients, recent studies point to the need of individualizing luteal phase support according to the needs of each patient.     

女性激素在胆囊胆固醇结石形成中的作用的研究现状

目的综述女性激素致胆囊胆固醇结石形成的机制,为预防雌、孕激素致石形成寻找途径。方法复习有关雌、孕激素致石形成的文献,总结其致石机制。结果雌激素主要通过核效应机制影响胆固醇代谢导致胆固醇结石形成,也可通过非核效应促使胆固醇成核及影响胆汁排空参与结石形成。孕激素通过核效应机制影响介导胆囊平滑肌收缩舒张的G蛋白α亚基损伤胆囊运动,通过非核效应途径影响离子通道及信号传导削弱胆囊运动,但孕酮的非核效应在结石形成中可能不起重要作用。结论女性激素致石机制复杂,明确其相关致石机制可为预防雌、孕激素致石形成开辟新途径。     

Peptidoglycan inhibits progesterone and androstenedione production in bovine ovarian theca cells

Uterine bacterial infection perturbs uterine and ovarian functions in postpartum dairy cows. Peptidoglycan (PGN) produced by gram-positive bacteria has been shown to disrupt the ovarian function in ewes. The aim of this study was to determine the effect of PGN on steroid production in bovine theca cells at different stages of follicular development. Bovine theca cells isolated from pre- and post-selection ovarian follicles (<8.5 mm and >8.5 mm in diameter, respectively) were cultured in vitro and challenged with PGN. Steroid production was evaluated by measuring progesterone (P4) and androstenedione (A4) concentration in culture media after 48 h or 96 h of culture. Bovine theca cells expressed PGN receptors including Toll-like receptor 2 and nucleotide-binding oligomerization domain 1 and 2. Treatment with PGN (1, 10, or 50 μg/ml) led to a decrease in P4 and A4 production by theca cells in both pre- and post-selection follicles. The mRNA expression of steroidogenic enzymes were decreased by PGN treatment. Moreover, A4 production was further suppressed when theca cells of post-selection follicles were simultaneously treated by PGN and lipopolysaccharide (0.1, 1, or 10 μg/ml). These findings indicate that bacterial toxins may act locally on ovarian steroidogenic cells and compromise follicular development in postpartum dairy cows.