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dihydrotestosterone

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https://www.readbyqxmd.com/read/28346887/high-resolution-mass-spectrometry-as-an-alternative-detection-method-to-tandem-mass-spectrometry-for-the-analysis-of-endogenous-steroids-in-serum
#1
Federico Ponzetto, Julien Boccard, Norbert Baume, Tiia Kuuranne, Serge Rudaz, Martial Saugy, Raul Nicoli
Recently, steroid hormones quantification in blood showed a promising ability to detect testosterone doping and interesting complementarities with the urinary module of the Athlete Biological Passport (ABP). In this work, an ultra-high pressure liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) method was developed for the quantification of eleven endogenous steroids in serum. The performance of the full scan and targeted SIM acquisition modes was evaluated and compared to the performance of tandem mass spectrometry (MS/MS)...
March 18, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28345462/functional-interaction-of-fibroblast-growth-factor-8b-and-androgen-in-prostate-cancer-cell-proliferation
#2
Wen-Jun Xiao, Gui-Ming Zhang, Ding-Wei Ye
Fibroblast growth factor 8b and androgen play important roles in cell proliferation of prostate cancer. We investigated the effects of fibroblast growth factor 8b and androgen on the proliferation of prostate cell lines and the corresponding intracellular mechanisms. It is found that dihydrotestosterone and fibroblast growth factor 8b stimulated Lncap cell mitosis in a concentration-responsive manner, with 30 ng/mL as the most suitable concentration, respectively. Dihydrotestosterone treatment alone did not enhance the expression and phosphorylation level of fibroblast growth factor receptor but significantly enhanced the level of fibroblast growth factor receptor phosphorylation elicited by fibroblast growth factor 8b...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28344042/exercise-differentially-affects-metabolic-functions-and-white-adipose-tissue-in-female-letrozole-and-dihydrotestosterone-induced-mouse-models-of-polycystic-ovary-syndrome
#3
Rodrigo R Marcondes, Manuel Maliqueo, Romina Fornes, Anna Benrick, Min Hu, Niklas Ivarsson, Mattias Carlström, Samuel W Cushman, Karin G Stenkula, Gustavo A R Maciel, Elisabet Stener-Victorin
Here we hypothesized that exercise in dihydrotestosterone (DHT) or letrozole (LET)-induced polycystic ovary syndrome mouse models improves impaired insulin and glucose metabolism, adipose tissue morphology, and expression of genes related to adipogenesis, lipid metabolism, Notch pathway and browning in inguinal and mesenteric fat. DHT-exposed mice had increased body weight, increased number of large mesenteric adipocytes. LET-exposed mice displayed increased body weight and fat mass, decreased insulin sensitivity, increased frequency of small adipocytes and increased expression of genes related to lipolysis in mesenteric fat...
March 24, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28324051/androgen-stimulates-growth-of-mouse-preantral-follicles-in-vitro-interaction-with-follicle-stimulating-hormone-and-with-growth-factors-of-the-tgf%C3%AE-superfamily
#4
Mhairi Laird, Kacie Thomson, Mark Fenwick, Jocelyn Mora, Stephen Franks, Kate Hardy
Androgens are essential for the normal function of mature antral follicles but also have a role in the early stages of follicle development. Polycystic ovary syndrome (PCOS), the commonest cause of anovulatory infertility, is characterized by androgen excess and aberrant follicle development that includes accelerated early follicle growth. We have examined the effects of testosterone and dihydrotestosterone (DHT) on development of isolated mouse preantral follicles in culture with the specific aims of investigating interaction with FSH, the steroidogenic pathway and with growth factors of the TGFβ superfamily that are known to have a role in early follicle development...
January 24, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324045/ring-finger-protein-6-mediates-androgen-induced-granulosa-cell-proliferation-and-follicle-growth-via-modulation-of-androgen-receptor-signaling
#5
Jung Jin Lim, Chae Young Han, Dong Ryul Lee, Benjamin K Tsang
The destiny of the ovarian follicle (growth or atresia) is tightly regulated by actions and interactions of endocrine, paracrine and autocrine factors. Although androgens are known to be important in the regulation of folliculogenesis, whether they facilitate or suppress follicular growth has been controversial and the mechanisms involved are not fully understood. Moreover, the role and regulation of its receptor (AR) in mediating androgen signaling during follicular development is not clear. Here, we report that the active androgen dihydrotestosterone (DHT) up-regulates the expression of AR and its E3 ligase Ring Finger Protein 6 (RNF6), increasing site-specific AR polyubiquitination and AR transcriptional activity for sKit-L expression in preantral follicle growth...
January 30, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324044/inverse-regulation-of-dht-synthesis-enzymes-5%C3%AE-reductase-types-1-and-2-by-the-androgen-receptor-in-prostate-cancer
#6
Étienne Audet-Walsh, Tracey Yee, Ingrid S Tam, Vincent Giguère
5α-reductase types 1 and 2, encoded by SRD5A1 and SRD5A2, are the two enzymes that can catalyze the conversion of testosterone to dihydrotestosterone, the most potent androgen receptor (AR) agonist in prostate cells. 5α-reductase type 2 is the predominant isoform expressed in the normal prostate. However, its expression decreases during prostate cancer (PCa) progression, while SRD5A1 increases and the mechanism underlying this transcriptional regulatory switch is still unknown. Interrogation of SRD5A mRNA expression in three publicly available datasets confirmed that SRD5A1 is increased in primary and metastatic PCa compared to non-tumoral prostate tissues, while SRD5A2 is decreased...
January 23, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323036/targeting-androgen-receptor-versus-targeting-androgens-to-suppress-castration-resistant-prostate-cancer
#7
Changcheng Guo, Shuyuan Yeh, Yuanjie Niu, Gonghui Li, Junhua Zheng, Lei Li, Chawnshang Chang
Prostate cancer (PCa) is the 2nd leading cause of cancer-related death among men in the United States and its progression is tightly associated with the androgen/androgen receptor (AR) signals. Men castrated before puberty (eunuchs) or men with inherited deficiency of type II 5α-reductase (with failure to convert testosterone to the more potent dihydrotestosterone) (DHT) do not develop PCa. To date, androgen deprivation therapy (ADT) with anti-androgen treatments to reduce or prevent androgens from binding to the AR remains the main therapeutic option for advanced PCa since its discovery by Huggins and Hodges in 1941...
March 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28320971/neuroendocrine-androgen-action-is-a-key-extraovarian-mediator-in-the-development-of-polycystic-ovary-syndrome
#8
Aimee S L Caldwell, Melissa C Edwards, Reena Desai, Mark Jimenez, Robert B Gilchrist, David J Handelsman, Kirsty A Walters
Polycystic ovary syndrome (PCOS) is a complex hormonal disorder characterized by reproductive, endocrine, and metabolic abnormalities. As the origins of PCOS remain unknown, mechanism-based treatments are not feasible and current management relies on treatment of symptoms. Hyperandrogenism is the most consistent PCOS characteristic; however, it is unclear whether androgen excess, which is treatable, is a cause or a consequence of PCOS. As androgens mediate their actions via the androgen receptor (AR), we combined a mouse model of dihydrotestosterone (DHT)-induced PCOS with global and cell-specific AR-resistant (ARKO) mice to investigate the locus of androgen actions that mediate the development of the PCOS phenotype...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28319389/potential-antiosteoporotic-natural-product-lead-compounds-that-inhibit-17%C3%AE-hydroxysteroid-dehydrogenase-type-2
#9
Anna Vuorinen, Roger T Engeli, Susanne Leugger, Fabio Bachmann, Muhammad Akram, Atanas G Atanasov, Birgit Waltenberger, Veronika Temml, Hermann Stuppner, Liselotte Krenn, Sylvin B Ateba, Dieudonné Njamen, Rohan A Davis, Alex Odermatt, Daniela Schuster
17β-Hydroxysteroid dehydrogenase type 2 (17β-HSD2) converts the active steroid hormones estradiol, testosterone, and 5α-dihydrotestosterone into their weakly active forms estrone, Δ(4)-androstene-3,17-dione, and 5α-androstane-3,17-dione, respectively, thereby regulating cell- and tissue-specific steroid action. As reduced levels of active steroids are associated with compromised bone health and onset of osteoporosis, 17β-HSD2 is considered a target for antiosteoporotic treatment. In this study, a pharmacophore model based on 17β-HSD2 inhibitors was applied to a virtual screening of various databases containing natural products in order to discover new lead structures from nature...
March 20, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28300564/contrasting-roles-of-the-abcg2-q141k-variant-in-prostate-cancer
#10
Kathryn M Sobek, Jessica L Cummings, Dean J Bacich, Denise S O'Keefe
ABCG2 is a membrane transport protein that effluxes growth-promoting molecules, such as folates and dihydrotestosterone, as well as chemotherapeutic agents. Therefore it is important to determine how variants of ABCG2 affect the transporter function in order to determine whether modified treatment regimens may be necessary for patients harboring ABCG2 variants. Previous studies have demonstrated an association between the ABCG2 Q141K variant and overall survival after a prostate cancer diagnosis. We report here that in patients with recurrent prostate cancer, those who carry the ABCG2 Q141K variant had a significantly shorter time to PSA recurrence post-prostatectomy than patients homozygous for wild-type ABCG2 (P=0...
March 11, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28294070/dutasteride-in-androgenetic-alopecia-an-update
#11
Tasleem Arif, Konchok Dorjay, Mohammad Adil, Marwa Sami
BACKGROUND: Androgenetic alopecia is a common condition characterized by thinning of scalp hair. Conversion of testosterone to dihydrotestosterone, a more potent androgen, by the enzyme 5-a-reductase is responsible for underlying pathogenesis. Dutasteride, a synthetic 4-azasteroid, is a selective and competitive inhibitor of both type-1 and type-2 isoenzymes of 5-alpha-reductase. Finasteride and minoxidil are the only approved drugs for androgenetic alopecia. Dutasteride has been demonstrated to be effective in several randomized, double-blind, placebo controlled trials in androgenetic alopecia...
March 10, 2017: Current Clinical Pharmacology
https://www.readbyqxmd.com/read/28293633/combined-ligand-structure-based-virtual-screening-and-molecular-dynamics-simulations-of-steroidal-androgen-receptor-antagonists
#12
Yuwei Wang, Rui Han, Huimin Zhang, Hongli Liu, Jiazhong Li, Huanxiang Liu, Paola Gramatica
The antiandrogens, such as bicalutamide, targeting the androgen receptor (AR), are the main endocrine therapies for prostate cancer (PCa). But as drug resistance to antiandrogens emerges in advanced PCa, there presents a high medical need for exploitation of novel AR antagonists. In this work, the relationships between the molecular structures and antiandrogenic activities of a series of 7α-substituted dihydrotestosterone derivatives were investigated. The proposed MLR model obtained high predictive ability...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28274349/sex-hormones-and-acne
#13
Qiang Ju, Tao Tao, Tingting Hu, Ayşe Serap Karadağ, Safaa Al-Khuzaei, WenChieh Chen
The skin is an endocrine organ with the expression of metabolizing enzymes and hormone receptors for diverse hormones. The sebaceous gland is the main site of hormone biosynthesis, especially for androgens, and acne is the classical androgen-mediated dermatosis. In sebocytes, conversion of 17-hydroxyprogesterone directly to dihydrotestosterone bypassing testosterone has been demonstrated, while type II 17β-hydroxysteroid dehydrogenase can inactivate the action of testosterone and dihydrotestosterone. The androgen receptor-dependent genomic effect of dihydrotestosterone on sebocytes is confirmed...
March 2017: Clinics in Dermatology
https://www.readbyqxmd.com/read/28261839/clinical-and-molecular-characteristics-in-15-patients-with-androgen-receptor-gene-mutations-from-south-china
#14
L Su, J Cheng, X Yin, G Liu, Z Lu, H Sheng, Y Cai, Q Shi, L Liu
A variety of mutations in the androgen receptor (AR) gene are linked to androgen insensitivity syndrome (AIS) or sexual development disorder. Here, we studied 15 patients with various degrees of disorders of genital hypoplasia from South China. Clinical data including basal hormone level, phenotype, karyotyping and SRY gene identification were documented. Exons with flanking intronic region of the AR gene were sequenced and analysed for mutations, and a total of eight mutations were identified in the AR gene...
March 6, 2017: Andrologia
https://www.readbyqxmd.com/read/28253524/intracrine-androgen-biosynthesis-in-renal-cell-carcinoma
#15
Geun Taek Lee, Christopher S Han, Young Suk Kwon, Rutveej Patel, Parth K Modi, Seok Joo Kwon, Izak Faiena, Neal Patel, Eric A Singer, Han-Jong Ahn, Wun-Jae Kim, Isaac Y Kim
BACKGROUND: Renal cell carcinoma (RCC) is one of the most lethal genitourinary cancers. The presence of androgen receptor (AR) in RCC has recently been shown to be associated with higher tumour stage irrespective of gender. Because the clinical context of androgens in female RCC patients is similar to that of prostate cancer patients undergoing androgen-deprivation therapy, mechanisms underlying the emergence of castration-resistant prostate cancer (CRPC) may be at play in AR-positive RCC cells...
March 2, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28250347/synthesis-biological-evaluation-and-molecular-docking-of-avicequinone-c-analogues-as-potential-steroid-5%C3%AE-reductase-inhibitors
#16
Wiranpat Karnsomwan, Ponsawan Netcharoensirisuk, Thanyada Rungrotmongkol, Wanchai De-Eknamkul, Supakarn Chamni
Avicequinone C (5a), a furanonaphthoquinone isolated from the Thai mangrove Avicennia marina has been shown previously to have interesting steroid 5α-reductase type 1 inhibitory activity. In this study, a series of avicequinone C analogues containing furanonaphthoquinone with different degrees of saturation and substituents at the furan ring were synthesized. The resulting synthetic avicequinone C and analogues (5a-f) along with some related compounds including 2,5-dihydroxy-1,4-benzoquinone (6) and natural naphthoquinones such as lawsone (7a) and lapachol (7b) were evaluated for their in vitro cell viability and steroid 5α-reductase type 1 inhibitory activities using the cultured cell line of human keratinocytes (HaCaT)...
2017: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28245981/rapid-uptake-biotransformation-esterification-and-lack-of-depuration-of-testosterone-and-its-metabolites-by-the-common-mussel-mytilus-spp
#17
Tamar I Schwarz, Ioanna Katsiadaki, Benjamin H Maskrey, Alexander P Scott
The presence of the vertebrate steroids, testosterone (T) and 17β-estradiol in mollusks is often cited as evidence that they are involved in the control of their reproduction. In this paper, we show that a likely source of T in at least one species, the common mussel (Mytilus spp.), is from uptake from water. When mussels were exposed to waterborne tritiated T ([(3)H]-T) in a closed container, the radioactivity decreased rapidly and exponentially until, by 24h, approximately 35% remained in the water. The rate of uptake of radiolabel could not be saturated by concentrations as high as 16...
February 27, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28241109/sex-steroid-hormones-in-relation-to-barrett-s-esophagus-an-analysis-of-the-finbar-study
#18
M B Cook, S Wood, P L Hyland, P Caron, J Drahos, R T Falk, R M Pfeiffer, S M Dawsey, C C Abnet, P R Taylor, C Guillemette, L J Murray, L A Anderson
Previously, we observed strong positive associations between circulating concentrations of free testosterone and free dihydrotestosterone (DHT) in relation to Barrett's esophagus in a US male military population. To replicate these findings, we conducted a second study of sex steroid hormones and Barrett's esophagus in the Factors Influencing the Barrett/Adenocarcinoma Relationship (FINBAR) Study based in Northern Ireland and Ireland. We used mass spectrometry to quantitate EDTA plasma concentrations of nine sex steroid hormones and ELISA to quantitate sex hormone-binding globulin in 177 male Barrett's esophagus cases and 185 male general population controls within the FINBAR Study...
March 2017: Andrology
https://www.readbyqxmd.com/read/28240250/regulation-of-tfpi%C3%AE-expression-by-mir-27a-b-3p-in-human-endothelial-cells-under-normal-conditions-and-in-response-to-androgens
#19
Ana B Arroyo, Salam Salloum-Asfar, Carlos Pérez-Sánchez, Raúl Teruel-Montoya, Silvia Navarro, Nuria García-Barberá, Ginés Luengo-Gil, Vanessa Roldán, John-Bjarne Hansen, Chary López-Pedrera, Vicente Vicente, Rocío González-Conejero, Constantino Martínez
The increased risk of cardiovascular events in older men is multifactorial, but the significant reduction of testosterone levels has been involved. As this hormone regulates the expression of TFPI by unknown mechanisms, we aimed to evaluate the role of miRNAs in the regulation of TFPIα expression under normal conditions and in response to androgens. In silico studies allowed the selection of 4 miRNAs as potential TFPIα regulators. Only miR-27a/b-3p significantly reduced TFPIα expression in two endothelial cell lines...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28236045/detection-and-quantification-of-12-anabolic-steroids-and-analogs-in-human-whole-blood-and-20-in-hair-using-lc-hrms-ms-application-to-real-cases
#20
Nicolas Fabresse, Stanislas Grassin-Delyle, Isabelle Etting, Jean-Claude Alvarez
We developed and validated a method to detect and quantify 12 anabolic steroids in blood (androstenedione, dihydrotestosterone, boldenone, epitestosterone, mesterolone, methandienone, nandrolone, stanozolol, norandrostenedione, tamoxifene, testosterone, trenbolone) and eight more in hair samples (nandrolone phenylpropionate, nandrolone decanoate, testosterone propionate, testosterone benzoate, testosterone cypionate, testosterone decanoate, testosterone phenylpropionate, testosterone undecanoate) using liquid chromatography coupled to high-resolution mass spectrometry...
February 24, 2017: International Journal of Legal Medicine
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