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https://www.readbyqxmd.com/read/28445889/genetic-polymorphisms-in-aromatase-cyp19a1-are-not-associated-with-gonadal-phenotypes-in-red-eared-slider-turtle-hatchlings-developed-at-a-pivotal-temperature
#1
Yuiko Matsumoto, David Crews
Embryonic gonad sex in many reptilian species is determined by the incubation temperature of the egg, a differentiation process known as temperature-dependent sex determination (TSD). Incubation at the pivotal temperature (PvT) results in approximately an equal number of offspring of both sexes. We investigated the potential contribution of genetic variations that drives the gonadal differentiation into testes or ovaries under this temperature in the red-eared slider turtle (Trachemys scripta). Four male and 4 female hatchlings of eggs that had been incubated at the PvT were examined for polymorphisms at an approximately 23-kb region of the aromatase (cyp19a1) gene...
April 27, 2017: Sexual Development: Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation
https://www.readbyqxmd.com/read/28442777/serotonin-transporter-deficiency-drives-estrogen-dependent-obesity-and-glucose-intolerance
#2
Weibin Zha, Horace T B Ho, Tao Hu, Mary F Hebert, Joanne Wang
Depression and use of antidepressant medications are both associated with increased risk of obesity, potentially attributed to a reduced serotonin transporter (SERT) function. However, how SERT deficiency promotes obesity is unknown. Here, we demonstrated that SERT (-/-) mice display abnormal fat accumulation in both white and brown adipose tissues, glucose intolerance and insulin resistance while exhibiting suppressed aromatase (Cyp19a1) expression and reduced circulating 17β-estradiol levels. 17β-estradiol replacement in SERT (-/-) mice reversed the obesity and glucose intolerance, supporting a role for estrogen in SERT deficiency-associated obesity and glucose intolerance...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28442026/neuromodulatory-effect-of-oestradiol-in-the-metabolism-of-ovarian-progesterone-and-oestradiol-during-dioestrus-ii-participation-of-the-superior-mesenteric-ganglion
#3
Adriana Vega Orozco, Cynthia Bronzi, Sandra Vallcaneras, Zulema Sosa, Marilina Casais
The aims of the present study were to determine: (1) whether oestradiol (E2) in the superior mesenteric ganglion (SMG) modifies the release of ovarian progesterone (P4), androstenedione (A2) and E2, the activity and gene expression of 3β-hydroxysteroid dehydrogenase (3β-HSD) and 20α-HSD and the expression of P450 aromatase (Cyp19a1) and (2) whether any such modifications are related to changes in ovarian nitric oxide (NO) and noradrenaline (NA) levels during dioestrus II. Using an ex vivo SMG-ovarian nervous plexus-ovary system, ovarian P4 release was measured following the addition E2 plus tamoxifen (Txf) (10-6M) to the ganglion, whereas A2, E2, NA and NO were measured following the addition of E2 alone...
April 26, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28429243/slco1b1-polymorphisms-and-plasma-estrone-conjugates-in-postmenopausal-women-with-er-%C3%A2-breast-cancer-genome-wide-association-studies-of-the-estrone-pathway
#4
Tanda M Dudenkov, James N Ingle, Aman U Buzdar, Mark E Robson, Michiaki Kubo, Irada Ibrahim-Zada, Anthony Batzler, Gregory D Jenkins, Tracy L Pietrzak, Erin E Carlson, Poulami Barman, Matthew P Goetz, Donald W Northfelt, Alvaro Moreno-Aspita, Clark V Williard, Krishna R Kalari, Yusuke Nakamura, Liewei Wang, Richard M Weinshilboum
BACKGROUND: Estrone (E1), the major circulating estrogen in postmenopausal women, promotes estrogen-receptor positive (ER+) breast tumor growth and proliferation. Two major reactions contribute to E1 plasma concentrations, aromatase (CYP19A1) catalyzed E1 synthesis from androstenedione and steroid sulfatase (STS) catalyzed hydrolysis of estrone conjugates (E1Cs). E1Cs have been associated with breast cancer risk and may contribute to tumor progression since STS is expressed in breast cancer where its activity exceeds that of aromatase...
April 20, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28423275/single-or-multiple-access-channels-to-the-cyp450s-active-site-an-answer-from-free-energy-simulations-of-the-human-aromatase-enzyme
#5
Alessandra Magistrato, Jacopo Sgrignani, Rolf Krause, Andrea Cavalli
Cytochromes P450 (CYP450s), in particular, CYP19A1 and CYP17A1, are key clinical targets of breast and prostate anticancer therapies, critical players in drug metabolism, and their overexpression in tumors is associated with drug resistance. In these enzymes, ligand (substrates, drugs) metabolism occurs in deeply buried active sites accessible only via several grueling channels, whose exact biological role remains unclear. Gaining direct insights on the mechanism by which ligands travel in and out is becoming increasingly important given that channels are involved in the modulation of binding/dissociation kinetics and the specificity of ligands toward a CYP450...
April 24, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28414904/in-silico-prediction-of-chemicals-binding-to-aromatase-with-machine-learning-methods
#6
Hanwen Du, Yingchun Cai, Hongbin Yang, Hongxiao Zhang, Yuhan Xue, Guixia Liu, Yun Tang, Weihua Li
Environmental chemicals may affect endocrine systems through multiple mechanisms, one of which is via effects on aromatase (also known as CYP19A1), an enzyme critical for maintaining the normal balance of estrogens and androgens in the body. Therefore, rapid and efficient identification of aromatase-related endocrine disrupting chemicals (EDCs) is important for toxicology and environment risk assessment. In this study, on the basis of the Tox21 10K compound library, in silico classification models for predicting aromatase binders/nonbinders were constructed by machine learning methods...
April 26, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28412504/endotoxin-induced-tlr4-signaling-downregulates-cyp19a1-expression-through-cebpb-in-buffalo-granulosa-cells
#7
Vengala Rao Yenuganti, Ravinder, Dheer Singh
Estrogen is essential for growth and development of ovarian follicles. Infections associated with E. coli or Endotoxin (LPS) suppress estradiol production by the downregulation of CYP19A1 expression. However, the molecular mechanism of its down regulation is not yet known. To elucidate the molecular mechanisms of LPS-mediated downregulation of CYP19A1 gene expression, we studied the effect of LPS and TLR4 signaling pathway inhibitor (OxPAPC, OxPAPC-Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine) on CYP19A1 expression, and expression of CEBPB and CEBPB binding on CYP19A1 proximal promoter (CYP19A1 PII) in buffalo granulosa cells in vitro...
April 13, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28410957/fetal-alpha-5-reductase-val89leu-mutation-is-associated-with-late-miscarriage
#8
Beatriz Pérez-Nevot, Jose-Luis Royo, Miriam Cortés, Ana M Lendínez, Arturo Reyes-Palomares, Ana-José Jiménez, Maximiliano Ruiz-Galdón, Armando Reyes-Engel
The present study was undertaken to determine the role of different polymorphisms affecting the testosterone/oestrogen pathway in miscarriage. Alpha 5-reductase (SRD5A2) rs523349 and rs9282858, cytochrome P450 aromatase (CYP19A1) rs4646, rs10046 and rs2236722 and oestrogen receptor (ESR1) rs9340799, rs2234693 and rs6932902 polymorphisms were selected. The case group consisted of 94 samples of formalin-fixed and paraffin-embedded fetal tissue from a miscarriage at ≤24 weeks. The control group comprised a population of 331 young healthy subjects...
March 21, 2017: Reproductive Biomedicine Online
https://www.readbyqxmd.com/read/28403774/pharmacogenetics-of-aromatase-inhibitors-in-endocrine-responsive-breast-cancer-lessons-learnt-from-tamoxifen-and-cyp2d6-genotyping
#9
Karin Jeanne Baatjes, Magda Conradie, Justus Paul Apffelstaedt, Maritha Kotze
BACKGROUND: Genetics play a significant role in drug metabolism of endocrine therapy of breast cancer. These aspects have been studied extensively in patients on tamoxifen, but the pharmacogenetics of aromatase inhibitors are less established. In contrast to the protective effect of tamoxifen, aromatase inhibitors are linked with an increased risk for bone loss and fractures. OBJECTIVE: This review outlines key issues around implementation of pharmacogenetics of cytochrome P450 and tamoxifen as a model for optimal use of aromatase inhibitors in postmenopausal women with estrogen receptor positive breast cancer...
April 12, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28400072/notch-signaling-pathway-promotes-the-development-of-ovine-ovarian-follicular-granulosa-cells
#10
Jiongjie Jing, Xiaolong Jiang, Jianwei Chen, Xiaolei Yao, Miaomiao Zhao, Pengfei Li, Yangyang Pan, Youshe Ren, Wenzhong Liu, Lihua Lyu
The Notch signaling pathway regulates cell proliferation, differentiation and apoptosis involved in development of the organs and tissues such as nervous system, cartilage, lungs, kidneys and prostate as well as the ovarian follicles. This study aimed to investigate the mRNA expression and localization of NOTCH2, as the key factor in Notch signaling pathway. This was determined by PCR, real-time PCR and immunohistochemistry. Additionally, the effects of inhibiting Notch signaling pathway with different concentrations (5μM, 10μM and 20μM) of N-[N-(3, 5-Difuorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT), an inhibitor of Notch signaling pathway, on ovine granulosa cells was determined in vitro by detecting estradiol production using enzyme linked immunosorbent assay and expressions of the genes related to the cell cycle and apoptosis using real-time polymerase chain reaction (PCR)...
March 28, 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28397603/masculinization-related-genes-and-cell-mass-structures-during-early-gonadal-differentiation-in-the-african-clawed-frog-xenopus-laevis
#11
Mikako Wada, Kazuko Fujitani, Kei Tamura, Shuuji Mawaribuchi, Yosuke Kamata, Nobuhiko Takamatsu, Michihiko Ito
The African clawed frog Xenopus laevis has a female heterogametic ZZ/ZW-type sex-determining system. We previously discovered a W-linked female sex-determining gene dm-W that is involved in ovary formation, probably through the up-regulation of the estrogen synthesis genes cyp19a1 and foxl2. We also reported that a unique "mass-in-line structure", which disappears from ZZ gonads during early testicular development, might serve as the basis for ovary differentiation in ZW gonads. However, the molecular mechanisms underlying early masculinization are poorly understood...
April 2017: Zoological Science
https://www.readbyqxmd.com/read/28383663/transcriptomic-analysis-of-gene-cascades-involved-in-protein-kinase-a-and-c-signalling-in-the-kgn-line-of-human-ovarian-granulosa-tumour-cells1
#12
Patricia G Tremblay, Marc-André Sirard
The developmental competence of an oocyte is its capacity to resume maturation, undergo successful fertilization and reach the blastocyst stage. This competence is acquired through interaction with somatic cells of the follicle. Cumulus and granulosa cells support oocyte development while the oocyte influences follicular cell growth and differentiation. Studies suggest that follicle-stimulating hormone and luteinizing hormone play an essential role in oocyte competence acquisition through signalling initiated by protein kinases A and C (PKA and PKC) in granulosa cells...
April 5, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28381288/maternal-urinary-phthalates-and-sex-specific-placental-mrna-levels-in-an-urban-birth-cohort
#13
Jennifer J Adibi, Jessie P Buckley, Myoung Keun Lee, Paige L Williams, Allan C Just, Yaqi Zhao, Hari K Bhat, Robin M Whyatt
BACKGROUND: Prenatal urinary concentrations of phthalates in women participants in an urban birth cohort were associated with outcomes in their children related to neurodevelopment, autoimmune disease risk, and fat mass at 3,5,7, and 8 years of life. Placental biomarkers and outcomes at birth may offer biologic insight into these associations. This is the first study to address these associations with candidate genes from the phthalate and placenta literature, accounting for sex differences, and using absolute quantitation methods for mRNA levels...
April 5, 2017: Environmental Health: a Global Access Science Source
https://www.readbyqxmd.com/read/28348070/syndecan-1-represses-cell-growth-and-fsh-responsiveness-in-human-granulosa-cells
#14
Simon Colombe, Laura Houllier, Emmanuelle Fleurot, Guénaëlle Levallet, Annie BenhaÏm, Pierre-Jacques Bonnamy, Jerome Levallet
Albeit devoid of intrinsic catalytic activity, the transmembrane heparan sulfate proteoglycan syndecan 1 plays critical roles in cellular processes such as extracellular matrix crosstalk, cytoskeletal organization, cell spreading, proliferation and differentiation. During the ovarian cycle, the expression of syndecan 1 in granulosa cells shows cyclic variation suggesting that it might fulfil specific roles in follicle development. To investigate its physiological roles on granulosa cells, syndecan 1 was overexpressed in human granulosa cell line KGN which retains features of granulosa cells from small antral follicle such as estradiol (E2) synthesis and low expression of functional FSH receptor (FSHR)...
March 27, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28347743/transcription-of-cyp19a1-is-directly-regulated-by-sf-1-in-the-theca-cells-of-ovary-follicles-in-chicken
#15
Jing Wang, Yanzhang Gong
Many studies have suggested the important role of estrogen in ovarian differentiation and development of vertebrates including chicken. Cytochrome P450 aromatase, encoded by CYP19A1, is a key enzyme in estrogen synthesis, but the mechanism of CYP19A1 regulation in chicken remains unknown. Here, we found that CYP19A1 was only expressed in the theca cell layers of chicken ovary follicles. Steroidogenic factor 1 (SF-1, also named as nuclear receptor subfamily 5 group A member 1, NR5A1), a potential regulators, was expressed in both the theca cell layers and granulosa cell layers...
March 24, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28346074/germline-genetic-predictors-of-aromatase-inhibitor-concentrations-estrogen-suppression-and-drug-efficacy-and-toxicity-in-breast-cancer-patients
#16
Daniel L Hertz, N Lynn Henry, James M Rae
The third-generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, are highly effective for the treatment of estrogen receptor-positive breast cancer in postmenopausal women. AIs inhibit the aromatase (CYP19A1)-mediated production of estrogens. Most patients taking AIs achieve undetectable blood estrogen concentrations resulting in drug efficacy with tolerable side effects. However, some patients have suboptimal outcomes, which may be due, in part, to inherited germline genetic variants...
March 27, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28345956/modulation-of-steroidogenesis-by-vitamin-d3-in-granulosa-cells-of-the-mouse-model-of-polycystic-ovarian-syndrome
#17
Shabnam Bakhshalizadeh, Fardin Amidi, Ashraf Alleyassin, Masoud Soleimani, Reza Shirazi, Maryam Shabani Nashtaei
Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of women of reproductive age characterized by polycystic ovarian morphology, anovulation or oligomenorrhea, and hyperandrogenism. It is shown that disruption in the steroidogenesis pathway caused by excess androgen in PCOS is a critical element of abnormal folliculogenesis and failure in dominant follicle selection. Vitamin D plays an important role in the regulation of ovulatory dysfunction and can influence genes involved in steroidogenesis in granulosa cells...
June 2017: Systems Biology in Reproductive Medicine
https://www.readbyqxmd.com/read/28337462/time-and-dose-dependent-effects-of-17-beta-estradiol-on-short-term-real-time-proliferation-and-gene-expression-in-porcine-granulosa-cells
#18
Sylwia Ciesiółka, Joanna Budna, Karol Jopek, Artur Bryja, Wiesława Kranc, Sylwia Borys, Michal Jeseta, Adrian Chachuła, Agnieszka Ziółkowska, Paweł Antosik, Dorota Bukowska, Klaus P Brüssow, Małgorzata Bruska, Michał Nowicki, Maciej Zabel, Bartosz Kempisty
The key mechanisms responsible for achievement of full reproductive and developmental capability in mammals are the differentiation and transformation of granulosa cells (GCs) during folliculogenesis, oogenesis, and oocyte maturation. Although the role of 17 beta-estradiol (E2) in ovarian activity is widely known, its effect on proliferative capacity, gap junction connection (GJC) formation, and GCs-luteal cells transformation requires further research. Therefore, the goal of this study was to assess the real-time proliferative activity of porcine GCs in vitro in relation to connexin (Cx), luteinizing hormone receptor (LHR), follicle stimulating hormone receptor (FSHR), and aromatase (CYP19A1) expression during short-term (168 h) primary culture...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28296881/transcriptomic-responses-to-environmental-temperature-by-turtles-with-temperature-dependent-and-genotypic-sex-determination-assessed-by-rnaseq-inform-the-genetic-architecture-of-embryonic-gonadal-development
#19
Srihari Radhakrishnan, Robert Literman, Jennifer Neuwald, Andrew Severin, Nicole Valenzuela
Vertebrate sexual fate is decided primarily by the individual's genotype (GSD), by the environmental temperature during development (TSD), or both. Turtles exhibit TSD and GSD, making them ideal to study the evolution of sex determination. Here we analyze temperature-specific gonadal transcriptomes (RNA-sequencing validated by qPCR) of painted turtles (Chrysemys picta TSD) before and during the thermosensitive period, and at equivalent stages in soft-shell turtles (Apalone spinifera-GSD), to test whether TSD's and GSD's transcriptional circuitry is identical but deployed differently between mechanisms...
2017: PloS One
https://www.readbyqxmd.com/read/28277108/temporal-effects-of-human-chorionic-gonadotropin-on-expression-of-the-circadian-genes-and-steroidogenesis-related-genes-in-human-luteinized-granulosa-cells
#20
Minghui Chen, Yanwen Xu, Benyu Miao, Hui Zhao, Jun Gao, Canquan Zhou
OBJECTIVE: It has been shown in animal models that circadian clock exists in corpora luteum which is essential for maintaining pregnancy. However, it is unknown whether circadian clock exists in corpora luteum and its relation with steroidogenesis in human ovary. STUDY DESIGN: Human luteinized granulosa cells from patients who underwent in vitro fertilization treatment were purified and cultured in vitro. Accumulation patterns of circadian gene and steroidogenesis-related gene mRNAs in human luteinized granulosa cells were observed during the 48 hours after treatment with human chorionic gonadotropin (hCG) by quantitative PCR...
March 5, 2017: Gynecological Endocrinology
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