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https://www.readbyqxmd.com/read/29031687/structure-function-relationships-for-the-selective-inhibition-of-human-3%C3%AE-hydroxysteroid-dehydrogenase-type-1-by-a-novel-androgen-analog
#1
Jenny H Pham, Catherine M Will, Vance L Mack, Matthew Halbert, Edward Alexander Conner, Kevin M Bucholtz, James L Thomas
3β-hydroxysteroid dehydrogenase type 1 (3β-HSD1) is selectively expressed in human placenta, mammary glands and breast tumors in women. Human 3β-HSD2 is selectively expressed in adrenal glands and ovaries. Based on AutoDock 3 and 4 results, we have exploited key differences in the amino acid sequences of 3β-HSD1 (Ser194, Arg195) and 3β-HSD2 (Gly194, Pro195) by designing a selective inhibitor of 3β-HSD1. 2,16-Dicyano-4,5-epoxy-androstane-3,17-dione (16-cyano-17-keto-trilostane or DiCN-AND) was synthesized in a 4-step procedure from androstenedione...
October 11, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28989885/impact-of-severity-of-illness-on-the-function-of-the-hypothalamo-pituitary-gonadal-axis-in-postmenopausal-women-with-acute-severe-illness-implications-for-predicting-disease-outcome
#2
Suresh Vaikkakara, Marella Neelima Raj, Alok Sachan, Alladi Mohan, Bhuma Vengamma, P V L N Srinivas Rao, Arun Mukka, Chiruvella Sravani, Amaresh P Reddy
BACKGROUND: While elevated levels of estradiol were predictive of mortality in critically ill surgical and trauma patients, their ability to predict outcome in nonsurgical patients has not been studied. We aimed to study the determinants of gonadotropin levels in acutely ill postmenopausal women with nonsurgical disease and the impact of changes in the gonadal axis on the outcome of these patients. METHODS: Thirty-five postmenopausal women admitted to medical intensive care with acute severe illness and having a Simplified Acute Physiology Score (SAPS II score) ≥30 (in-hospital mortality rate ≥ 10%) were recruited...
September 2017: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28973534/genomic-effects-of-androstenedione-and-sex-specific-liver-cancer-susceptibility-in-mice
#3
John P Rooney, Natalia Ryan, Brian N Chorley, Susan D Hester, Elaina M Kenyon, Judith E Schmid, Barbara Jane George, Michael F Hughes, Yusupha M Sey, Alan Tennant, Denise K MacMillan, Jane Ellen Simmons, Charlene A McQueen, Arun Pandiri, Charles E Wood, J Christopher Corton
Current strategies for predicting carcinogenic mode of action for non-genotoxic chemicals are based on identification of early key events in toxicity pathways. The goal of this study was to evaluate short-term key event indicators resulting from exposure to androstenedione (A4), an androgen receptor agonist and known liver carcinogen in mice. Liver cancer is more prevalent in men compared to women, but androgen-related pathways underlying this sex difference have not been clearly identified. Short-term hepatic effects of A4 were compared to reference agonists of the estrogen receptor (ethinyl estradiol, EE) and glucocorticoid receptor (prednisone, PRED)...
August 23, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28972875/effect-of-melatonin-on-bovine-theca-cells-in-vitro
#4
T Feng, L F Schutz, B C Morrell, M C Perego, L J Spicer
Melatonin affects granulosa cell function in several species but its function in theca cells is less clear, particularly in monotocous animals. Thus, the objectives of this study were to determine the effects of melatonin on theca cell steroidogenesis, gene expression and cell proliferation in a monotocous species, namely cattle. Ovaries were collected from a local bovine abattoir, from which theca cells were isolated from large (8-22mm) follicles and treated with various hormones in serum-free medium for 24h or 48h...
October 4, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28970799/altered-cyp19a1-and-cyp3a4-activities-due-to-mutations-a115v-t142a-q153r-and-p284l-in-the-human-p450-oxidoreductase
#5
Sameer S Udhane, Shaheena Parween, Norio Kagawa, Amit V Pandey
All cytochromes P450s in the endoplasmic reticulum rely on P450 oxidoreductase (POR) for their catalytic activities. Mutations in POR cause metabolic disorders of steroid hormone biosynthesis and affect certain drug metabolizing P450 activities. We studied mutations A115V, T142A, Q153R identified in the flavin mononucleotide (FMN) binding domain of POR that interacts with partner proteins and P284L located in the hinge region that is required for flexibility and domain movements in POR. Human wild-type (WT) and mutant POR as well as CYP3A4 and CYP19A1 proteins in recombinant form were expressed in bacteria, and purified proteins were reconstituted in liposomes for enzyme kinetic assays...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28950181/cross-sectional-study-of-the-determinants-and-associations-of-sex-hormone-binding-globulin-concentrations-in-first-degree-relatives-fdr-of-patients-with-type-2-diabetes-mellitus
#6
N A Abdella, O A Mojiminiyi
AIMS: This study explores the determinants of sex hormone binding globulin (SHBG) and associations with categories of glucose intolerance and undiagnosed diabetes in first-degree relatives (FDR) of patients with Type 2 Diabetes Mellitus (T2D). METHODS: Anthropometric indices, fasting lipids, glucose, insulin, adiponectin, leptin, SHBG, estradiol (E2), testosterone (TT), androstenedione (AND), dehydroepiandrosterone sulphate (DHEA-S), high-sensitivity C-reactive protein (hs-CRP) and alanine aminotransferase (ALT) were measured in 584 FDR...
September 5, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28948822/changes-to-fetal-steroidogenesis-caused-by-maternal-smoking
#7
K Adamcová, L Kolátorová, T Chlupáčová, M Šimková, H Jandíková, A Pařízek, L Stárka, M Dušková
Smoking during pregnancy presents health risks for both the mother and her child. In this study we followed changes in the production of steroid hormones in pregnant smokers. We focused on changes in steroidogenesis in the blood of mothers in their 37(th) week of pregnancy and in mixed cord blood from their newborns. The study included 88 healthy women with physiological pregnancies (17 active smokers and 71 non-smokers). We separately analyzed hormonal changes associated with smoking according to the sex of newborns...
September 26, 2017: Physiological Research
https://www.readbyqxmd.com/read/28941500/prostaglandin-d2-uses-components-of-ros-signaling-to-enhance-testosterone-production-in-keratinocytes
#8
Alon Mantel, J Tyson McDonald, Kennedy Goldsborough, Valerie M Harvey, Joanne Chan
Elevated levels of prostaglandin D2 (PGD2) have been shown to be present in the bald scalp of androgenic alopecia (AGA) patients and to functionally inhibit hair growth. However, its precise mechanism in AGA has yet to be clearly defined. Although testosterone plays a critical role in the initiation and progression of AGA, the existence of a possible link between PGD2 and testosterone in skin has not been investigated. Here we show that human keratinocytes treated with PGD2 show enhanced capacity to convert the weak androgen, androstenedione, to testosterone...
October 2017: Journal of Investigative Dermatology. Symposium Proceedings
https://www.readbyqxmd.com/read/28941255/effects-of-placebo-controlled-insulin-sensitizing-drugs-on-hormonal-parameters-in-polycystic-ovary-syndrome-patients-a-network-meta-analysis
#9
Yong-Hui Dai, Rong Huang, Peng-Fei Zhao, Jian-Hua Xu, Dong-Dong Liu, Fu-Dong Luo
This network meta-analysis was conducted to compare effects of different placebo-controlled insulin-sensitizing drugs, including metformin, pioglitazone, rosiglitazone and troglitazone on hormonal parameters in polycystic ovary syndrome (PCOS) patients. We searched PubMed, EMBASE and Cochrane Library databases from their inception to July 2017. Randomized controlled trials (RCTs) met our inclusion criteria were included. We combined direct and indirect evidences to evaluate weighted mean difference (WMD) value and draw surface under the cumulative ranking curve (SUCRA)...
September 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28939401/inefficient-ugt-conjugation-of-adrenal-11%C3%AE-hydroxyandrostenedione-metabolites-highlights-c11-oxy-c19-steroids-as-the-predominant-androgens-in-prostate-cancer
#10
Therina du Toit, Amanda C Swart
Although the adrenal C19 steroids, androstenedione and testosterone, contribute to prostate cancer (PCa) progression the full complement of adrenal androgens, including the C11-oxy C19 steroids, 11β-hydroxyandrostenedione (11OHA4) and 11β-hydroxytestosterone (11OHT) and their androgenic metabolites, 11keto-testosterone (11KT) and 11keto-dihydrotestosterone (11KDHT) have, to date, not been considered. This study investigated the contribution of 11OHA4 and 11OHT to the pool of active androgens in the prostate...
September 20, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28936565/development-of-macaque-secondary-follicles-exposed-to-neutral-red-prior-to-3-dimensional-culture
#11
Daiane L Bulgarelli, Alison Y Ting, Brenda J Gordon, Ana Carolina Japur de Sá Rosa-E-Silva, Mary B Zelinski
PURPOSE: Neutral red (NR) may assist identification of preantral follicles in pieces of cortical tissue prior to cryopreservation in cancer patients requesting fertility preservation. This study is the first to analyze this effect by follicle growth rate after long-term culture in primates. METHODS: Ovarian cortex was obtained from adult rhesus macaques, was cut into fragments, and was incubated with NR. Secondary follicles were readily visualized following NR staining and then were encapsulated into alginate beads and cultured individually for 4 weeks in αMEM media supplemented with 10 ng/ml FSH at 5% O2...
September 21, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28929436/endogenous-sex-hormone-exposure-and-repetitive-element-dna-methylation-in-healthy-postmenopausal-women
#12
Devon J Boyne, Christine M Friedenreich, John B McIntyre, Frank Z Stanczyk, Kerry S Courneya, Will D King
PURPOSE: Epigenetic mechanisms may help to explain the complex and heterogeneous relation between sex hormones and cancer. Few studies have investigated the effects of sex hormones on epigenetic markers related to cancer risk such as levels of methylation within repetitive DNA elements. Our objective was to describe the association between endogenous sex hormone exposure and levels of LINE-1 and Alu methylation in healthy postmenopausal women. METHODS: We nested a cross-sectional study within the Alberta Physical Activity and Breast Cancer Prevention Trial (2003-2006)...
September 19, 2017: Cancer Causes & Control: CCC
https://www.readbyqxmd.com/read/28918287/steroid-hormones-and-persistent-organic-pollutants-in-plasma-from-north-eastern-atlantic-pilot-whales
#13
Katrin S Hoydal, Bjarne Styrishave, Tomasz M Ciesielski, Robert J Letcher, Maria Dam, Bjørn M Jenssen
Persistent organic pollutants (POPs) are known to have endocrine disruptive effects, interfering with endogenous steroid hormones. The present study examined nine steroid hormones and their relationships with the concentrations of selected POPs in pilot whales (Globicephala melas) from the Faroe Islands, NE Atlantic. The different steroids were detected in 15 to all of the 26 individuals. High concentrations of progesterone (83.3-211.7pmol/g) and pregnenolone (PRE; 4.68-5.69pmol/g) were found in three adult females indicating that they were pregnant or ovulating...
November 2017: Environmental Research
https://www.readbyqxmd.com/read/28915398/masculinization-and-reproductive-effects-in-western-mosquitofish-gambusia-affinis-after-long-term-exposure-to-androstenedione
#14
Li-Ping Hou, Yang Yang, Hu Shu, Guang-Guo Ying, Jian-Liang Zhao, Gui-Zhen Fang, Li Xin, Wen-Jun Shi, Li Yao, Xue-Mei Cheng
Androstenedione (AED) is a naturally occurring steroid hormone. It is metabolized to potent androgens, which may induce androgenic effects in fish. However, little is known whether and how the androgens interfere with the fish gonadal development and reproduction. This study aimed at demonstrating the effects of long-term AED exposure on reproduction and development in mosquitofish (Gambusia affinis). The growth, development and several morphological endpoints, including the segment number and length of anal fin, histological changes of gonads and liver, were evaluated in mosquitofish during development from fertilized embryo to adulthood (180 days) after exposure of AED at environmentally relevant concentrations...
September 12, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28913143/role-of-osteocalcin-tumor-necrosis-factor-alpha-and-adiponectin-in-polycystic-ovary-syndrome-patients-with-insulin-resistance
#15
Gönül Erkan, Ahter Tanay Tayyar, Gökhan Açmaz, İptisam İpek Müderris, Gülden Başkol, Fahri Bayram
OBJECTIVE: Insulin resistance (IR) seems to be the main pathogenic factor in polycystic ovary syndrome (PCOS). Adiponectin and tumor necrosis factor-alpha (TNF-α) are important in IR. The aim of this study was to evaluate the correlations of osteocalcin, adiponectin, and TNF-α with IR in PCOS. MATERIALS AND METHODS: A total of 60 women were divided into two groups. The first group constituted 44 patients with PCOS and the control group comprised 16 healthy women...
June 2017: Turk J Obstet Gynecol
https://www.readbyqxmd.com/read/28912358/combined-oral-contraceptives-plus-spironolactone-compared-with-metformin-in-women-with-polycystic-ovary-syndrome-a-one-year-randomized-clinical-trial
#16
RANDOMIZED CONTROLLED TRIAL
Macarena Alpañés, Francisco Álvarez-Blasco, Elena Fernández-Durán, Manuel Luque-Ramírez, Héctor F Escobar-Morreale
OBJECTIVE: We aimed to compare a combined oral contraceptive (COC) plus the antiandrogen spironolactone with the insulin sensitizer metformin in women with polycystic ovary syndrome (PCOS). DESIGN: We conducted a randomized, parallel, open-label, clinical trial comparing COC (30 μg of ethinylestradiol and 150 μg of desogestrel) plus spironolactone (100 mg/day) with metformin (850 mg b.i.d.) for one year in women with PCOS (EudraCT2008-004531-38). METHODS: The composite primary outcome included efficacy (amelioration of hirsutism, androgen excess and menstrual dysfunction) and cardiometabolic safety (changes in the frequencies of disorders of glucose tolerance, dyslipidemia and hypertension)...
November 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28912339/reproductive-and-metabolic-features-during-puberty-in-sons-of-women-with-polycystic-ovary-syndrome
#17
Nicolás Crisosto, Bárbara Echiburú, Manuel Maliqueo, Marta Luchsinger, Pedro Rojas, Sergio Recabarren, Teresa Sir-Petermann
CONTEXT: Intrauterine life may be implicated in the origin of polycystic ovary syndrome (PCOS) modifying the endocrine and metabolic functions of children born to PCOS mothers independently of the genetic inheritance and gender. The aim of the present study was to evaluate the reproductive and metabolic functions in sons of women with PCOS during puberty. METHODS: Sixty-nine PCOS sons (PCOSs) and 84 control sons of 7-18 years old matched by the Tanner stage score were studied...
November 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28904054/a-13-steroid-serum-panel-based-on-lc-ms-ms-use-in-detection-of-adrenocortical-carcinoma
#18
David R Taylor, Lea Ghataore, Lewis Couchman, Royce P Vincent, Ben Whitelaw, Dylan Lewis, Salvador Diaz-Cano, Gabriele Galata, Klaus-Martin Schulte, Simon Aylwin, Norman F Taylor
BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignancy, with an annual incidence of 1 or 2 cases per million. Biochemical diagnosis is challenging because up to two-thirds of the carcinomas are biochemically silent, resulting from de facto enzyme deficiencies in steroid hormone biosynthesis. Urine steroid profiling by GC-MS is an effective diagnostic test for ACC because of its capacity to detect and quantify the increased metabolites of steroid pathway synthetic intermediates...
September 13, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28891949/isaria-fumosorosea-kch-j2-entomopathogenic-strain-as-an-effective-biocatalyst-for-steroid-compound-transformations
#19
Ewa Kozłowska, Monika Dymarska, Edyta Kostrzewa-Susłow, Tomasz Janeczko
The catalytic activity of enzymes produced by an entomopathogenic filamentous fungus (Isaria fumosorosea KCh J2) towards selected steroid compounds (androstenedione, adrenosterone, progesterone, 17α-methyltestosterone and dehydroepiandrosterone) was investigated. All tested substrates were efficiently transformed. The structure of the substrate has a crucial impact on regio- and stereoselectivity of hydroxylation since it affects binding to the active site of the enzyme. Androstenedione was hydroxylated in the 7α-position to give a key intermediate in the synthesis of the diuretic-7α-hydroxyandrost-4-ene-3,17-dione with 82% conversion...
September 9, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28888606/preovulatory-follicle-characteristics-and-oocyte-competence-in-repeat-breeder-dairy-cows
#20
P Sood, M Zachut, I Dekel, H Dube, S Jacoby, U Moallem
The varied and elusive etiology of repeat breeding (RB) in dairy cows necessitates evaluation of oocytes and follicles, which have not previously been assessed together. Accordingly, we evaluated characteristics of preovulatory follicles and the competence of oocytes in control (CTL) and RB cows. The estrous cycles of 35 cows (18 CTL and 17 RB) were synchronized using PGF2α and estrus detection. Cows with a corpus luteum were treated with PGF2α and, 14 to 15 d after a visible behavioral estrus, they were administered a second PGF2α, followed 48 h later by follicular fluid (FF) aspiration of the preovulatory follicles...
November 2017: Journal of Dairy Science
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