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https://www.readbyqxmd.com/read/28800957/insight-into-the-mode-of-action-and-selectivity-of-pbrm-a-covalent-steroidal-inhibitor-of-17%C3%AE-hydroxysteroid-dehydrogenase-type-1
#1
Alexandre Trottier, René Maltais, Diana Ayan, Xavier Barbeau, Jenny Roy, Martin Perreault, Richard Poulin, Patrick Lagüe, Donald Poirier
17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) is involved in the biosynthesis of estradiol, the major bioactive endogenous estrogen in mammals, and constitutes an interesting therapeutic target for estrogen-dependent diseases. A steroidal derivative, 3-{[(16β,17β)-3-(2-bromoethyl)-17-hydroxyestra-1,3,5(10)-trien-16-yl]methyl} benzamide (PBRM), has recently been described as a non-estrogenic, irreversible inhibitor of 17β-HSD1. However, the mode of action of this inhibitor and its selectivity profile have not yet been elucidated...
August 8, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28791837/the-role-of-17%C3%AE-estradiol-metabolites-in-chromium-induced-oxidative-stress
#2
Ewa Sawicka, Anna Długosz
BACKGROUND: The increasing incidence of estrogen-dependent breast cancer and the presence in the environment of a large number of factors that interact with estrogen receptors have sparked interest in chemical influences on estrogen-dependent processes. In a previous work, the authors examined the interaction of estradiol with chromium. In the present article the importance of estradiol biotransformation in these interactions is investigated. There is no information in the available literature about the role of metabolites in exposure to chromium...
March 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/28750898/the-use-of-a-unique-co-culture-model-of-fetoplacental-steroidogenesis-as-a-screening-tool-for-endocrine-disruptors-the-effects-of-neonicotinoids-on-aromatase-activity-and-hormone-production
#3
Elyse Caron-Beaudoin, Rachel Viau, Andrée-Anne Hudon-Thibeault, Cathy Vaillancourt, J Thomas Sanderson
Estrogen biosynthesis during pregnancy is dependent on the collaboration between the fetus producing the androgen precursors, and the placenta expressing the enzyme aromatase (CYP19). Disruption of estrogen production by contaminants may result in serious pregnancy outcomes. We used our recently developed in vitro co-culture model of fetoplacental steroidogenesis to screen the effects of three neonicotinoid insecticides on the catalytic activity of aromatase and the production of steroid hormones. A co-culture of H295R human adrenocortical carcinoma cells with fetal characteristics and BeWo human choriocarcinoma cells which display characteristics of the villous cytotrophoblast was exposed for 24h to various concentrations of three neonicotinoids: thiacloprid, thiamethoxam and imidacloprid...
July 24, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28694300/the-regulation-of-oxytocin-and-oxytocin-receptor-in-human-placenta-according-to-gestational-age
#4
Seung Chul Kim, Jae-Eon Lee, Seong Soo Kang, Hoe-Saeng Yang, Sun Suk Kim, Beum-Soo An
Oxytocin (OXT) is a peptide hormone that plays a central role in the regulation of parturition and lactation in the uterus. OXT signaling is mediated by OXT receptor (OXTR), which shows species- and tissue-specific expressions and gene regulation. In the present study, we examined synthesis of OXT and OXTR in human placenta tissue according to gestational age. A total of 48 placentas were divided into early preterm, late preterm, and term groups depending on gestational age, and expression of OXT and OXTR was evaluated...
July 10, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28669870/secretory-expression-purification-and-functional-characterization-of-17%C3%AE-hydroxysteroid-dehydrogenase-type-1-from-mammalian-hek293t-cells
#5
Jiong Chen, Wei Feng, Yue Zhao
17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) mainly catalyzes the reduction of estrone into estradiol. The enzymatic conversion is a critical step in estradiol accumulation in breast tissue, which is a valuable prognosis index of breast cancer disease. However, the source of 17β-HSD1 for inhibitor design is limited. In this study, the fragment encoding human 17β-HSD1 was successfully cloned and expressed in human embryonic kidney (HEK) 293T mammalian cells. The recombinant protein was purified by immobilized metal ion affinity chromatography yielding above 17 mg of purified 17β-HSD1 protein per liter of cell culture, with a specific activity of 8...
September 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28645573/evidence-that-fetal-death-is-associated-with-placental-aging
#6
Kaushik Maiti, Zakia Sultana, Robert J Aitken, Jonathan Morris, Felicity Park, Bronwyn Andrew, Simon C Riley, Roger Smith
BACKGROUND: The risk of unexplained fetal death or stillbirth increases late in pregnancy, suggesting that placental aging is an etiological factor. Aging is associated with oxidative damage to DNA, RNA, and lipids. We hypothesized that placentas at >41 completed weeks of gestation (late-term) would show changes consistent with aging that would also be present in placentas associated with stillbirths. OBJECTIVE: We sought to determine whether placentas from late-term pregnancies and unexplained stillbirth show oxidative damage and other biochemical signs of aging...
June 20, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28560047/effects-of-dexamethasone-on-progesterone-and-estrogen-profiles-and-uterine-progesterone-receptor-localization-during-pregnancy-in-sahel-goat-in-semi-arid-region
#7
Dauda Yahi, Nicholas Adetayo Ojo, Gideon Dauda Mshelia
BACKGROUND: Despite the widespread use of dexamethasone in veterinary and human medicine, it is reported to cause some severe pregnancy related side effects like abortion in some animals. The mechanism of the response is not clear but seems to be related to interspecies and/or breed difference in response which may involve alterations in the concentrations of some reproductive hormones. METHODS: Twenty Sahel goats comprising 18 does and 2 bucks were used for this study...
2017: Journal of Animal Science and Technology
https://www.readbyqxmd.com/read/28487135/estrogen-enhanced-apical-and-basolateral-secretion-of-apolipoprotein-b-100-by-polarized-trophoblast-derived-bewo-cells
#8
Miriam Kamper, Florian Mittermayer, Rosalinda Cabuk, Katharina Gelles, Isabella Ellinger, Marcela Hermann
Cholesterol is an important nutrient for fetal development and transplacental transport occurs at all stages of human pregnancy. Furthermore, cholesterol is required for membrane building as well as steroid hormone synthesis. Therefore, all placental cell types require cholesterol for proper function. In human term placenta, the syncytiotrophoblast (STB) faces the maternal circulation. Uptake of maternal-derived cholesterol at the apical membrane of the STB is well understood, but the route by which cholesterol exits at the basal side for subsequent transfer across the fetal endothelial cells (FEC) or to other placental cell types remains not well characterized...
July 2017: Biochimie
https://www.readbyqxmd.com/read/28454689/identification-of-appropriate-reference-genes-for-qpcr-analyses-of-placental-expression-of-slc7a3-and-induction-of-slc5a1-in-porcine-endometrium
#9
Chelsie B Steinhauser, Theodore T Wing, Haijun Gao, Xilong Li, Robert C Burghardt, Guoyao Wu, Fuller W Bazer, Greg A Johnson
INTRODUCTION: Endometria and placentae undergo developmental changes that affect the stability of genes used as references for normalization of qPCR data. We identified genes that are stable within the porcine endometrium and placenta throughout pregnancy, and elucidated the temporal/spatial mRNA localization of the glucose and arginine transporters, solute carrier family (SLC) 5A1 and SLC7A3, respectively. MATERIALS AND METHODS: qPCR was performed for 10 genes within porcine endometria from Days 5, 11, and 15 of the estrous cycle and 11, 15, 25, 40, 60, and 85 of pregnancy; and chorioallantois from Days 30, 35, 45, 50, 60, and 85...
April 2017: Placenta
https://www.readbyqxmd.com/read/28440394/g-protein-coupled-receptor-30-mediates-the-effects-of-estrogen-on-endothelial-cell-tube-formation-in%C3%A2-vitro
#10
Liyuan Zhou, Hong Chen, Xun Mao, Hongbo Qi, Philip N Baker, Hua Zhang
The placenta is the exchange organ between the mother and the fetus. The inadequate function of this organ is associated with a number of pregnancy disorders. Hypoxia and oxidative stress during placental development may induce endothelial dysfunction, resulting in the reduction in the perfusion of the placenta. During pregnancy, the levels of estrogen are increased. Decreased estrogen levels have been reported in women with preeclampsia. However, whether estrogen is involved in placental angiogenesis remains unclear...
June 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28324064/bmp7-induces-uterine-receptivity-and-blastocyst-attachment
#11
Diana Monsivais, Caterina Clementi, Jia Peng, Paul T Fullerton, Renata Prunskaite-Hyyryläinen, Seppo J Vainio, Martin M Matzuk
In women, the window of implantation is limited to a brief 2- to 3-day period characterized by optimal levels of circulating ovarian hormones and a receptive endometrium. Although the window of implantation is assumed to occur 8 to 10 days after ovulation in women, molecular markers of endometrial receptivity are necessary to determine optimal timing prior to embryo transfer. Previous studies showed that members of the bone morphogenetic protein (BMP) family are expressed in the uterus necessary for female fertility; however, the role of BMP7 during implantation and in late gestation is not known...
April 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323944/from-pregnancy-to-preeclampsia-a-key-role-for-estrogens
#12
REVIEW
Nadia Berkane, Philippe Liere, Jean-Paul Oudinet, Alexandre Hertig, Guillaume Lefèvre, Nicola Pluchino, Michael Schumacher, Nathalie Chabbert-Buffet
Preeclampsia (PE) results in placental dysfunction and is one of the primary causes of maternal and fetal mortality and morbidity. During pregnancy, estrogen is produced primarily in the placenta by conversion of androgen precursors originating from maternal and fetal adrenal glands. These processes lead to increased plasma estrogen concentrations compared with levels in nonpregnant women. Aberrant production of estrogens could play a key role in PE symptoms because they are exclusively produced by the placenta and they promote angiogenesis and vasodilation...
April 1, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/28259093/exposure-to-phytoestrogens-in-utero-and-age-at-menarche-in-a-contemporary-british-cohort
#13
Kristin J Marks, Terryl J Hartman, Ethel V Taylor, Michael E Rybak, Kate Northstone, Michele Marcus
Phytoestrogens are estrogenic compounds that occur naturally in plants. Phytoestrogens can cross the placenta, and animal studies have found associations between in utero exposure to phytoestrogens and markers of early puberty. We investigated the association between in utero exposure to phytoestrogens and early menarche (defined as <11.5 years of age at onset) using data from a nested case-control study within the Avon Longitudinal Study of Parents and Children, a longitudinal study involving families living in the South West of England...
May 2017: Environmental Research
https://www.readbyqxmd.com/read/28193709/testosterone-represses-estrogen-signaling-by-upregulating-mir-22-a-mechanism-for-imbalanced-steroid-hormone-production-in-preeclampsia
#14
Xuan Shao, Yanlei Liu, Ming Liu, Yongqing Wang, Liying Yan, Hao Wang, Liyang Ma, Yu-Xia Li, Yangyu Zhao, Yan-Ling Wang
Preeclampsia, a multisystem syndrome occurring during mid- to late gestation in humans, is a leading cause of maternal and perinatal morbidity and mortality. Patients usually present with high circulating testosterone and reduced estradiol production, but the mechanisms remain unclear. Revealing the mechanism that modulating the imbalance of testosterone and estradiol in preeclampsia is of great value in understanding the cause of the disease. The placenta is the predominant source of steroid hormone production during gestation, and we observed markedly increased 17β-HSD3 (17β-hydroxysteroid dehydrogenase 3) levels and downregulated aromatase expression, the key enzymes responsible for synthesis of testosterone and estradiol, respectively, in preeclamptic placentas compared with controls...
April 2017: Hypertension
https://www.readbyqxmd.com/read/28152429/synthesis-and-biological-evaluation-of-fluorinated-n-benzoyl-and-n-phenylacetoyl-derivatives-of-3-4-aminophenyl-coumarin-7-o-sulfamate-as-steroid-sulfatase-inhibitors
#15
Mateusz Daśko, Maja Przybyłowska, Janusz Rachon, Maciej Masłyk, Konrad Kubiński, Majus Misiak, Andrzej Składanowski, Sebastian Demkowicz
In the present work, we report convenient methods for the synthesis of 3-(4-aminophenyl)-coumarin-7-O-sulfamate derivatives N-acylated with fluorinated analogues of benzoic or phenylacetic acid as steroid sulfatase (STS) inhibitors. The design of these potential STS inhibitors was supported by molecular modeling techniques. Additionally, computational docking methods were used to determine the binding modes of the synthesized inhibitors and to identify potential interactions between inhibitors and amino acid residues located in the active site of STS...
March 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28089504/review-nutrient-sulfate-supply-from-mother-to-fetus-placental-adaptive-responses-during-human-and-animal-gestation
#16
REVIEW
P A Dawson, K Richard, A Perkins, Z Zhang, D G Simmons
Nutrient sulfate has numerous roles in mammalian physiology and is essential for healthy fetal growth and development. The fetus has limited capacity to generate sulfate and relies on sulfate supplied from the maternal circulation via placental sulfate transporters. The placenta also has a high sulfate requirement for numerous molecular and cellular functions, including sulfate conjugation (sulfonation) to estrogen and thyroid hormone which leads to their inactivation. Accordingly, the ratio of sulfonated (inactive) to unconjugated (active) hormones modulates endocrine function in fetal, placental and maternal tissues...
June 2017: Placenta
https://www.readbyqxmd.com/read/28008329/maternal-and-fetal-mechanisms-of-b-cell-regulation-during-pregnancy-human-chorionic-gonadotropin-stimulates-b-cells-to-produce-il-10%C3%A2-while-alpha-fetoprotein-drives-them-into-apoptosis
#17
Franziska Fettke, Anne Schumacher, Andrea Canellada, Natalia Toledo, Isabelle Bekeredjian-Ding, Albert Bondt, Manfred Wuhrer, Serban-Dan Costa, Ana Claudia Zenclussen
Maternal immune tolerance toward the fetus is an essential requisite for pregnancy. While T cell functions are well documented, little is known about the participation of B cells. We have previously suggested that IL-10-producing B cells are involved in pregnancy tolerance in mice and humans. By employing murine and human systems, we report now that fetal trophoblasts positively regulate the generation of IL-10-producing B cells. We next studied the participation of hormones produced by the placenta as well as the fetal protein alpha-fetoprotein (AFP) in B cell modulation...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27835804/gap-junctional-connexin-messenger-rna-expression-in-the-ovine-uterus-and-placenta-effects-of-estradiol-17%C3%AE-treatment-early-pregnancy-stages-and-embryo-origin
#18
M L Johnson, D A Redmer, L P Reynolds, A T Grazul-Bilska
Gap junctions play a major role in direct, contact-dependent cell-cell communication, and they have been implicated in the regulation of cellular metabolism and the coordination of cellular functions during growth and differentiation of organs and tissues. Gap junctional channels, composed of connexin (Cx) proteins, have been detected and shown to be influenced by hormones (eg, estrogen and progesterone) in uterine and placental tissues in several species. We hypothesized that (1) the messenger RNA (mRNA) for Cx26, Cx32, Cx37, and Cx43 is expressed in the uterus of ovariectomized sheep treated with estradiol-17β (E2) and in ovine placenta during early pregnancy, (2) E2-treatment of ovariectomized ewes would cause time-specific changes in Cx26, Cx32, Cx37, and Cx43 mRNA expression (experiment 1), and (3) expression of these 4 Cx would vary across the days of early pregnancy (experiment 2) and will be affected by embryo origin (ie, after application of assisted reproductive technologies [ARTs]; experiment 3)...
January 2017: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/27791094/primate-specific-mir-515-family-members-inhibit-key-genes-in-human-trophoblast-differentiation-and-are-upregulated-in-preeclampsia
#19
Ming Zhang, Sribalasubashini Muralimanoharan, Alison C Wortman, Carole R Mendelson
Dysregulation of human trophoblast invasion and differentiation can result in preeclampsia (PE), a hypertensive disorder of pregnancy with significant morbidity and mortality for mother and offspring. miRNA microarray analysis of RNA from human cytotrophoblasts (CytT), before and after differentiation to syncytiotrophoblast (SynT) in primary culture, revealed that members of miR-515 family-including miR-515-5p, miR-519e-5p, miR-519c-3p, and miR-518f, belonging to the primate- and placenta-specific chromosome 19 miRNA cluster (C19MC)-were significantly down-regulated upon human SynT differentiation...
October 24, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27761482/immunology-of-neuromyelitis-optica-during-pregnancy
#20
REVIEW
Vahid Davoudi, Kiandokht Keyhanian, Riley M Bove, Tanuja Chitnis
Anti-aquaporin-4 (AQP4) autoantibody plays a key role in the pathogenesis of neuromyelitis optica (NMO). Studies have shown increased relapse rates in patients with NMO during pregnancy and postpartum. High estrogen levels during pregnancy can increase activation-induced cytidine deaminase expression, which is responsible for immunoglobulin production. Additionally, sex hormones may influence antibody glycosylation, with effects on antibody function. Estrogen decreases apoptosis of self-reactive B cells, through upregulation of antiapoptotic molecules...
December 2016: Neurology® Neuroimmunology & Neuroinflammation
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