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androgen placenta

Thomas Mandel Clausen, Marina Ayres Pereira, Htoo Zarni Oo, Mafalda Resende, Tobias Gustavson, Yang Mao, Nobuo Sugiura, Janet Liew, Ladan Fazli, Thor G Theander, Mads Daugaard, Ali Salanti
In clinical oncology, diagnosis and evaluation of optimal treatment strategies are mostly based on histopathological examination combined with immunohistochemical (IHC) expression analysis of cancer-associated antigens in formalin fixed paraffin-embedded (FFPE) tissue biopsies. However, informative IHC analysis depends on both the specificity and affinity of the binding reagent, which are inherently difficult to quantify in situ. Here we describe a label-free method that allows for the direct and real-time assessment of molecular binding kinetics in situ on FFPE tissue specimens using quartz crystal microbalance (QCM) enabled biosensor technology...
July 2016: Sensing and Bio-Sensing Research
Andrea Olmos-Ortiz, Janice García-Quiroz, Rebeca López-Marure, Irma González-Curiel, Bruno Rivas-Santiago, Aleida Olivares, Euclides Avila, David Barrera, Ali Halhali, Felipe Caldiño, Fernando Larrea, Lorenza Díaz
Male fetus and neonates show increased immune vulnerability compared to females, which results in a higher risk of perinatal infections. These differences could partially be due to sex steroids differential modulation of vitamin D metabolism; since calcitriol, the most active vitamin D metabolite, regulates immune responses and transcriptionally induces the antimicrobial peptide cathelicidin in the human placenta. Calcitriol availability depends on CYP27B1 and CYP24A1 expression, the cytochromes involved in its synthesis and degradation, respectively...
October 2016: Journal of Steroid Biochemistry and Molecular Biology
Romina Fornes, Min Hu, Manuel Maliqueo, Milana Kokosar, Anna Benrick, David Carr, Håkan Billig, Thomas Jansson, Luigi Manni, Elisabet Stener-Victorin
Women with polycystic ovary syndrome (PCOS) have elevated circulating androgens during pregnancy and are at an increased risk of adverse pregnancy outcomes. Here we tested the hypotheses that maternal androgen excess decrease placental and fetal growth, and placental expression of markers of steroidogenesis, angiogenesis and sympathetic activity, and that acupuncture with low-frequency electrical stimulation prevents these changes. Pregnant rats were exposed to vehicle or testosterone on gestational day (GD)15-19...
September 15, 2016: Molecular and Cellular Endocrinology
Yves Morel, Florence Roucher, Ingrid Plotton, Claire Goursaud, Véronique Tardy, Delphine Mallet
Progesterone, estrogens, androgens and glucocorticoids are involved in pregnancy from implantation to parturition. Their biosynthesis and their metabolism result from complex pathways involving the fetus, the placenta and the mother. The absence of expression of some steroïdogenic enzymes as CYP17 in placenta and in adrenal fetal zone and the better determination of the onset and variation of others especially HSD3B2 during the pregnancy explain the production of the steroid hormones. Moreover the consequences of some disorders of steroidogenesis (especially aromatase, POR, CYP11A1 and 21-hydroxylase deficiencies) in fetus and mother during the pregnancy have permit to elucidate these complex pathways...
June 2016: Annales D'endocrinologie
Yixing Feng, Pin Zhang, Zhaobin Zhang, Jiachen Shi, Zhihao Jiao, Bing Shao
Triclosan (TCS) is a broad-spectrum antimicrobial agent that is frequently used in pharmaceuticals and personal care products. Reports have shown that TCS is a potential endocrine disruptor; however, the potential effects of TCS on placental endocrine function are unclear. The aim of this study was to investigate the endocrine disrupting effects of TCS on the placenta in pregnant rats. Pregnant rats from gestational day (GD) 6 to GD 20 were treated with 0, 30, 100, 300 and 600 mg/kg/d TCS followed by analysis of various biochemical parameters...
2016: PloS One
Susanne Lund Kristensen, Cecilia Høst Ramlau-Hansen, Erik Ernst, Sjurdur Frodi Olsen, Jens Peter Bonde, Anne Vested, Thorhallur Ingi Halldorsson, Panu Rantakokko, Hannu Kiviranta, Gunnar Toft
BACKGROUND: The biopersistent organochlorine pollutants dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB) and polychlorinated biphenyls (PCBs) can be detected in humans worldwide. The chemicals can cross the placenta and may interfere with endogenous hormonal homeostasis. OBJECTIVES: To investigate effects on female reproduction following intrauterine exposure to selected biopersistent organochlorines. METHODS: We used data from a Danish pregnancy cohort with follow-up on 436 eligible daughters at approximately 20years of age...
July 2016: Environment International
Wanhong He, Misra Gauri, Tang Li, Ruixuan Wang, Sheng-Xiang Lin
At the late 1940s, 17β-HSD1 was discovered as the first member of the 17β-HSD family with its gene cloned. The three-dimensional structure of human 17β-HSD1 is the first example of any human steroid converting enzyme. The human enzyme's structure and biological function have thus been studied extensively in the last two decades. In humans, the enzyme is expressed in placenta, ovary, endometrium and breast. The high activity of estrogen activation provides the basis of 17β-HSD1's implication in estrogen-dependent diseases, such as breast cancer, endometriosis and non-small cell lung carcinomas...
August 15, 2016: Gene
Sema Akçurin, Doğa Türkkahraman, Woo Young Kim, Erdem Durmaz, Jae Gook Shin, Su Jun Lee
OBJECTIVE: The CYP19A1 gene product aromatase is responsible for estrogen synthesis and androgen/estrogen equilibrium in many tissues, particularly in the placenta and gonads. Aromatase deficiency can cause various clinical phenotypes resulting from excessive androgen accumulation and insufficient estrogen synthesis during the pre- and postnatal periods. In this study, our aim was to determine the clinical characteristics and CYP19A1 mutations in three patients from a large Turkish pedigree...
June 5, 2016: Journal of Clinical Research in Pediatric Endocrinology
Christa E Flück, Amit V Pandey
Cytochrome P450 aromatase (CYP19A1), in human placenta metabolizes androgens to estrogens and uses reduced nicotinamide adenine dinucleotide phosphate through cytochrome P450 oxidoreductase (POR) for energy requirements for its metabolic activities. Mutations in the human POR lead to congenital adrenal hyperplasia due to loss of activities of several steroid metabolizing enzymatic reactions conducted by cytochrome P450 proteins located in the endoplasmic reticulum. Effect of POR mutations on different P450 activities depend on individual partner proteins...
March 23, 2016: Journal of Steroid Biochemistry and Molecular Biology
Shiwen Liu, Baiping Mao, Yanfang Bai, Jianpeng Liu, Huitao Li, Xiaoheng Li, Qingquan Lian, Ren-Shan Ge
Progesterone and estradiol produced by the human placenta are critical for maintenance of pregnancy and fetal development. In the human placenta, 3β-hydroxysteroid dehydrogenase 1 (HSD3B1) is responsible for the formation of progesterone from pregnenolone and aromatase (CYP19A1) for the production of estradiol from androgen. Insecticide methoxychlor (MXC) and its metabolite hydroxychlor (HPTE) may disrupt the activities of these 2 enzymes. In this study, we investigated the effects of MXC and HPTE on steroid production in human placental JEG-3 cells and on HSD3B1 and CYP19A1 activities...
2016: Pharmacology
Debashis Ghosh, Jessica Lo, Chinaza Egbuta
Human aromatase catalyzes the synthesis of estrogen from androgen with high substrate specificity. For the past 40 years, aromatase has been a target of intense inhibitor discovery research for the prevention and treatment of estrogen-dependent breast cancer. The so-called third generation aromatase inhibitors (AIs) letrozole, anastrozole, and the steroidal exemestane were approved in the U.S. in the late 1990s for estrogen-dependent postmenopausal breast cancer. Efforts to develop better AIs with higher selectivity and lower side effects were handicapped by the lack of an experimental structure of this unique P450...
June 9, 2016: Journal of Medicinal Chemistry
Tracey A Quinn, Udani Ratnayake, Hayley Dickinson, Margie Castillo-Melendez, David W Walker
Synthesis of dehydroepiandrosterone (DHEA) by the fetal adrenal gland is important for placental oestrogen production, and may also be important for modulating the effects of glucocorticoids on the developing brain. We have preciously shown that the enzymes and accessory proteins needed for DHEA synthesis-cytochrome P450 enzyme 17α-hydroxylase/17,20 lyase (P450c17), cytochrome-b5 (Cytb5), 3β-hydroxysteroid dehydrogenase (3βHSD)-are expressed in the adrenal gland from 30 days gestation, and DHEA, cortisol and aldosterone are present in fetal plasma from this time...
June 2016: Journal of Steroid Biochemistry and Molecular Biology
Alejandra Perez-Sepulveda, Lara J Monteiro, Aneta Dobierzewska, Pedro P España-Perrot, Pía Venegas-Araneda, Alejandra M Guzmán-Rojas, María I González, Macarena Palominos-Rivera, Carlos E Irarrazabal, Horacio Figueroa-Diesel, Manuel Varas-Godoy, Sebastián E Illanes
INTRODUCTION: Preeclampsia is a maternal hypertensive disorder with uncertain etiology and a leading cause of maternal and fetal mortality worldwide, causing nearly 40% of premature births delivered before 35 weeks of gestation. The first stage of preeclampsia is characterized by reduction of utero-placental blood flow which is reflected in high blood pressure and proteinuria during the second half of pregnancy. In human placenta androgens derived from the maternal and fetal adrenal glands are converted into estrogens by the enzymatic action of placental aromatase...
2015: PloS One
Emily S Barrett, Shanna H Swan
Prenatal stress is known to alter hypothalamic-pituitary-adrenal axis activity, and more recent evidence suggests that it may also affect androgen activity. In animal models, prenatal stress disrupts the normal surge of testosterone in the developing male, whereas in females, associations differ by species. In humans, studies show that (1) associations between prenatal stress and child outcomes are often sex-dependent, (2) prenatal stress predicts several disorders with notable sex differences in prevalence, and (3) prenatal exposure to stressful life events may be associated with masculinized reproductive tract development and play behavior in girls...
October 2015: Endocrinology
Iwona Wieciech, Małgorzata Grzesiak, Katarzyna Knapczyk-Stwora, Anna Pytlik, Maria Słomczynska
The study focuses on the expression of connexin 43 (Cx43), a gap junctional protein in the porcine placenta and uterus. The aim was to examine Cx43 mRNA and protein expression after antiandrogen flutamide treatment. Flutamide was injected into pregnant gilts at a daily dose of 50 mg/kg body weight at different stages of pregnancy: between days 43-49 (50 dpc), 83-89 (90 dpc) and 101-107 (108 dpc) of gestation. The animals were sacrificed and tissues were collected one day after the last injection. Cx43 immunostaining was observed in epithelial and stromal cells of the fetal part of the placenta; luminal and glandular epithelial cells of maternal part of the placenta and myometrium of the uterus within placentation sites...
2014: Folia Biologica (Krakow)
Juan P Arrebola, José M Molina-Molina, Mariana F Fernández, Jose M Sáenz, Esperanza Amaya, Paolo Indiveri, Elizabeth M Hill, Martin Scholze, Frances Orton, Andreas Kortenkamp, Nicolás Olea
It has been hypothesized that the rise in male reproductive disorders over recent decades may at least be partially attributable to environmental factors, including chemical exposures, but observed associations with single chemicals were rather weak. The aim of this case-control study was to explore the relationship between exposure to mixtures of (anti-)androgenic chemicals during pregnancy and the risk of cryptorchidism and/or hypospadias in offspring, using the total effective xenobiotic burden of anti-androgens (TEXB-AA) as a biomarker...
June 2015: Reproduction: the Official Journal of the Society for the Study of Fertility
Ellane R Cleys, Jennifer L Halleran, Vanessa A Enriquez, Juliano C da Silveira, Rachel C West, Quinton A Winger, Russell V Anthony, Jason E Bruemmer, Colin M Clay, Gerrit J Bouma
Sex steroid hormones regulate developmental programming in many tissues, including programming gene expression during prenatal development. While estradiol is known to regulate placentation, little is known about the role of testosterone and androgen signaling in placental development despite the fact that testosterone rises in maternal circulation during pregnancy and in placenta-induced pregnancy disorders. We investigated the role of testosterone in placental gene expression, and focused on androgen receptor (AR)...
2015: PloS One
Chan Jong Kim
Congenital lipoid adrenal hyperplasia (lipoid CAH) is the most fatal form of CAH, as it disrupts adrenal and gonadal steroidogenesis. Most cases of lipoid CAH are caused by recessive mutations in the gene encoding steroidogenic acute regulatory protein (StAR). Affected patients typically present with signs of severe adrenal failure in early infancy and 46,XY genetic males are phenotypic females due to disrupted testicular androgen secretion. The StAR p.Q258X mutation accounts for about 70% of affected alleles in most patients of Japanese and Korean ancestry...
December 2014: Annals of Pediatric Endocrinology & Metabolism
Susanne Weber, Joshua K Salabei, Gabriele Möller, Elisabeth Kremmer, Aruni Bhatnagar, Jerzy Adamski, Oleg A Barski
Aldo-keto reductases (AKRs) comprise a superfamily of proteins involved in the reduction and oxidation of biogenic and xenobiotic carbonyls. In humans, at least 15 AKR superfamily members have been identified so far. One of these is a newly identified gene locus, AKR1B15, which clusters on chromosome 7 with the other human AKR1B subfamily members (i.e. AKR1B1 and AKR1B10). We show that alternative splicing of the AKR1B15 gene transcript gives rise to two protein isoforms with different N termini: AKR1B15.1 is a 316-amino acid protein with 91% amino acid identity to AKR1B10; AKR1B15...
March 6, 2015: Journal of Biological Chemistry
Chih-Ping Chen, Tsang-Ming Ko, Chen-Yu Chen, Tao-Yeuan Wang, Schu-Rern Chern, Yu-Ling Kuo, Wayseen Wang
OBJECTIVE: To present first-trimester molecular diagnosis of complete hydatidiform mole (CHM) associated with dizygotic twin pregnancy conceived by intrauterine insemination. MATERIALS AND METHODS: A 32-year-old woman presented to the hospital with a huge complex cystic mass measuring about 8.5 cm × 4.1 cm in the uterine cavity and a living co-existing fetus with fetal biometry equivalent to 9 weeks. She underwent chorionic villus sampling at 13 weeks of gestation, and microsatellite genotyping for molar pregnancy test was applied...
December 2014: Taiwanese Journal of Obstetrics & Gynecology
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