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https://www.readbyqxmd.com/read/28716218/the-risk-of-dementia-with-the-use-of-5-alpha-reductase-inhibitors
#1
Blayne Welk, Eric McArthur, Michael Ordon, Sarah A Morrow, Jade Hayward, Stephanie Dixon
INTRODUCTION: There has been considerable interest in the interplay between testosterone and cognition. Dihydrotestosterone (DHT), which has been correlated with cognitive function, is significantly reduced with the use of 5 alpha reductase inhibitors (5ARI) for prostatic enlargement. Our objective was to assess whether the use of 5ARIs was associated with an increased risk of incident dementia. METHODS: We used a matched cohort design and linked administrative data from the province of Ontario, Canada...
August 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28711501/comparing-the-androgenic-and-estrogenic-properties-of-progestins-used-in-contraception-and-hormone-therapy
#2
Renate Louw-du Toit, Meghan S Perkins, Janet P Hapgood, Donita Africander
Progestins used in endocrine therapies bind to multiple steroid receptors and are associated with several side-effects. It is thus important to understand the relationship between steroid receptor cross-reactivity and the side-effect profile of progestins. In cell lines that express negligible levels of steroid receptors, we report for the first time the binding affinities, potencies and efficacies of selected progestins from different generations determined in parallel. We show that the progestins bind to the androgen receptor (AR) with similar affinities to each other and progesterone, while none bind estrogen receptor (ER)-β, and only norethisterone acetate, levonorgestrel and gestodene bind ERα...
July 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28711355/characterization-of-the-foxl2-proximal-promoter-and-coding-sequence-from-the-common-snapping-turtle-chelydra-serpentina
#3
Lei Guo, Turk Rhen
Sex is determined by temperature during embryogenesis in snapping turtles, Chelydra serpentina. Previous studies in this species show that dihydrotestosterone (DHT) induces ovarian development at temperatures that normally produce males or mixed sex ratios. The feminizing effect of DHT is associated with increased expression of FoxL2, suggesting that androgens regulate transcription of FoxL2. To test this hypothesis, we cloned the proximal promoter (1.6kb) and coding sequence for snapping turtle FoxL2 (tFoxL2) in frame with mCherry to produce a fluorescent reporter...
July 12, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28710978/relationships-between-pops-biometrics-and-circulating-steroids-in-male-polar-bears-ursus-maritimus-from-svalbard
#4
Tomasz M Ciesielski, Ingunn Tjelta Hansen, Jenny Bytingsvik, Martin Hansen, Elisabeth Lie, Jon Aars, Bjørn M Jenssen, Bjarne Styrishave
The aim of this study was to determine the effects of persistent organic pollutants (POPs) and biometric variables on circulating levels of steroid hormones (androgens, estrogens and progestagens) in male polar bears (Ursus maritimus) from Svalbard, Norway (n = 23). Levels of pregnenolone (PRE), progesterone (PRO), androstenedione (AN), dehydroepiandrosterone (DHEA), testosterone (TS), dihydrotestosterone (DHT), estrone (E1), 17α-estradiol (αE2) and 17β-estradiol (βE2) were quantified in polar bear serum by gas chromatography tandem mass spectrometry (GC-MS/MS), while POPs were measured in plasma...
July 12, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28706210/regulation-of-aromatase-expression-in-the-anterior-amygdala-of-the-developing-mouse-brain-depends-on-er%C3%AE-and-sex-chromosome-complement
#5
Carla Daniela Cisternas, Lucas Ezequiel Cabrera Zapata, María Angeles Arevalo, Luis Miguel Garcia-Segura, María Julia Cambiasso
During development sex differences in aromatase expression in limbic regions of mouse brain depend on sex chromosome factors. Genes on the sex chromosomes may affect the hormonal regulation of aromatase expression and this study was undertaken to explore that possibility. Male E15 anterior amygdala neuronal cultures expressed higher levels of aromatase (mRNA and protein) than female cultures. Furthermore, treatment with oestradiol (E2) or dihydrotestosterone (DHT) increased Cyp19a1 expression and aromatase protein levels only in female neuronal cultures...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28701684/expression-of-aldo-keto-reductase-family-1-member-c14-during-ovulation-in-the-rat
#6
Phuong T M Dam, You-Jee Jang, Ja-Yeon Kim, Seul-Gee Choi, Jae-Il Park, Young-Woo Seo, Sang-Young Chun
The potent androgen 5α-dihydrotestosterone is metabolized to the weak androgen 5α-androstane-3α, 17β-diol (3α-diol) by the enzyme aldo-keto reductase family 1, member C14 (Akr1c14) in rodents. The purpose of the present study was to investigate the regulation of Akr1c14 expression during the ovulatory process in rat ovaries. Northern blot analysis revealed that treatment of immature rats with equine chorionic gonadotropin resulted in lowered Akr1c14 expression, whereas subsequent treatment with human chorionic gonadotropin (hCG) increased ovarian Akr1c14 expression within 3 h...
July 11, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28689207/design-of-finasteride-loaded-nanoparticles-for-potential-treatment-of-alopecia
#7
Luís V Roque, Inês S Dias, Nuno Cruz, Ana Rebelo, Amílcar Roberto, Patrícia Rijo, Catarina P Reis
BACKGROUND/AIMS: Androgenetic alopecia is an extremely common dermatological disorder affecting both men and women. Oral finasteride (FNS), a synthetic 4-aza-3-oxosteroid compound with poor aqueous solubility, blocks the peripheral conversion of testosterone to dihydrotestosterone (DHT) in a significant reduction in DHT concentration, achieving satisfactory results in alopecia treatment. However, its oral intake generally causes severe side effects. Considering that there is currently no scientifically proven treatment, new drug delivery systems able to improve alopecia therapy are urgently required...
July 8, 2017: Skin Pharmacology and Physiology
https://www.readbyqxmd.com/read/28687384/the-identification-of-new-substrates-of-human-dhrs7-by-molecular-modeling-and-in-vitro-testing
#8
Lucie Zemanová, Palani Kirubakaran, Ignacio Hernando Pato, Hana Štambergová, Jiří Vondrášek
Human DHRS7 (SDR34C1) is one of insufficiently described enzymes of the short-chain dehydrogenase/reductase superfamily. The members of this superfamily often play an important pato/physiological role in the human body, participating in the metabolism of diverse substrates (e.g. retinoids, steroids, xenobiotics). A systematic approach to the identification of novel, physiological substrates of DHRS7 based on a combination of homology modeling, structure-based virtual screening and experimental evaluation has been used...
July 4, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28684382/a-regulatory-role-of-androgen-in-ovarian-steroidogenesis-by-rat-granulosa-cells
#9
Toru Hasegawa, Yasuhiko Kamada, Takeshi Hosoya, Shiho Fujita, Yuki Nishiyama, Nahoko Iwata, Yuji Hiramatsu, Fumio Otsuka
Excess androgen and insulin-like growth factor (IGF)-I in the ovarian follicle has been suggested to be involved in the pathophysiology of polycystic ovary syndrome (PCOS). Here we investigated the impact of androgen and IGF-I on the regulatory mechanism of ovarian steroidogenesis using rat primary granulosa cells. It was revealed that androgen treatment with dihydrotestosterone (DHT) amplified progesterone synthesis in the presence of FSH and IGF-I, whereas it had no significant effect on estrogen synthesis by rat granulosa cells...
July 3, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28673432/pharmacokinetics-clinical-efficacy-safety-profile-and-patient-reported-outcomes-in-patients-receiving-subcutaneous-testosterone-pellets-900-mg-for-treatment-of-symptoms-associated-with-androgen-deficiency
#10
Chris G McMahon, Neil Shusterman, Brian Cohen
BACKGROUND: Implantation of testosterone doses of at least 150 to 450 mg (ie, two to six pellets) is common clinical practice despite a lack of prospective data. AIM: To evaluate pharmacokinetics, clinical efficacy, safety, and patient-reported outcomes in men with androgen deficiency who received implantation of testosterone pellets (900 mg) in an open-label study. METHODS: Men with androgen deficiency (serum testosterone < 300 ng/dL [10...
July 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/28673330/udp-glucuronosyltransferases-and-biochemical-recurrence-in-prostate-cancer-progression
#11
Delores J Grant, Zinan Chen, Lauren E Howard, Emily Wiggins, Amanda De Hoedt, Adriana C Vidal, Skyla T Carney, Jill Squires, Clara E Magyar, Jiaoti Huang, Stephen J Freedland
BACKGROUND: Uridine 5'-diphosphate-glucuronosyltransferase 2B (UGT2B) genes code for enzymes that catalyze the clearance of testosterone, dihydrotestosterone (DHT), and DHT metabolites in the prostate basal and luminal tissue. The expression of the UGT2B15, UGT2B17, and UGT2B28 enzymes has not been evaluated in prostate tissue samples from hormone therapy-naïve patients. METHODS: We determined the expression of UGT2B15, UGT2B17, and UGT2B28 enzymes in 190 prostate tissue samples from surgical specimens of a multiethnic cohort of patients undergoing radical prostatectomy at the Durham Veterans Affairs Medical Center...
July 3, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28663228/testicular-versus-adrenal-sources-of-hydroxyandrogens-in-prostate-cancer
#12
Tianzhu Zang, Mary-Ellen Taplin, Daniel Tamae, Wanling Xie, Clementina Mesaros, Zhenwei Zhang, Glenn J Bubley, Robert Bruce Montgomery, Steven Balk, Elahe Mostaghel, Ian A Blair, Trevor Penning
Neoadjuvant androgen deprivation therapy (NADT) is one strategy for the treatment of early-stage prostate cancer; however, the long-term outcomes of NADT with radical prostatectomy including biochemical failure-free survival are not promising. One proposed mechanism is incomplete androgen ablation. In this study, we aimed to evaluate the efficiency of serum hydroxy-androgen suppression in patients with localized high-risk prostate cancer under NADT (leuprolide acetate plus abiraterone acetate and prednisone) and interrogate the primary sources of circulating hydroxy-androgens using our recently described stable isotope dilution liquid chromatography mass spectrometric method (Zang et al...
June 29, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28656662/greater-physical-activity-and-higher-androgen-concentrations-are-independently-associated-with-lower-cardiometabolic-risk-in-men
#13
Lauren C Chasland, Matthew W Knuiman, Mark L Divitini, Yi X Chan, David J Handelsman, Louise H Naylor, Daniel J Green, Bu B Yeap
CONTEXT: Male ageing is associated with lower circulating testosterone (T) and increased incidence of cardiovascular disease (CVD). Whether physical activity (PA) interacts with hormones to modify CVD risk is unclear. OBJECTIVE: We assessed whether PA and sex hormone concentrations were independently associated with measures of CVD risk. PARTICIPANTS: 1,649 men. METHODS: Leisure, home, work and total PA were ascertained...
June 28, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28645930/genomic-and-non-genomic-effects-of-androgens-in-the-cardiovascular-system-clinical-implications
#14
REVIEW
Angela K Lucas-Herald, Rheure Alves-Lopes, Augusto C Montezano, S Faisal Ahmed, Rhian M Touyz
The principle steroidal androgens are testosterone and its metabolite 5α-dihydrotestosterone (DHT), which is converted from testosterone by the enzyme 5α-reductase. Through the classic pathway with androgens crossing the plasma membrane and binding to the androgen receptor (AR) or via mechanisms independent of the ligand-dependent transactivation function of nuclear receptors, testosterone induces genomic and non-genomic effects respectively. AR is widely distributed in several tissues, including vascular endothelial and smooth muscle cells...
July 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28645211/akr1c3-mediated-adipose-androgen-generation-drives-lipotoxicity-in-women-with-polycystic-ovary-syndrome
#15
Michael W O'Reilly, Punith Kempegowda, Mark Walsh, Angela E Taylor, Konstantinos N Manolopoulos, J William Allwood, Robert K Semple, Daniel Hebenstreit, Warwick B Dunn, Jeremy W Tomlinson, Wiebke Arlt
Context: Polycystic ovary syndrome (PCOS) is a prevalent metabolic disorder, occurring in up to 10% of women of reproductive age. PCOS is associated with insulin resistance and cardiovascular risk. Androgen excess is a defining feature of PCOS and has been suggested as causally associated with insulin resistance; however, mechanistic evidence linking both is lacking. We hypothesized that adipose tissue is an important site linking androgen activation and metabolic dysfunction in PCOS...
June 22, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28639228/role-of-20-hydroxyeicosatetraenoic-acid-20-hete-in-androgen-mediated-cell-viability-in-prostate-cancer-cells
#16
Cecilia Colombero, Daniela Papademetrio, Paula Sacca, Eduardo Mormandi, Elida Alvarez, Susana Nowicki
20-Hydroxyeicosatetraenoic acid (20-HETE) is generated intracellularly through the ω-hydroxylation of arachidonic acid by the cytochrome P450 (in humans, CYP4A11 and CYP4F2). 20-HETE induces mitogenic responses in different cancer cells. The aim of this study was to analyze how 20-HETE impacts cell survival, proliferation, and apoptosis in prostate cancer cells. Incubation of the human androgen-sensitive cells (LNCaP) with 1-10 μM HET0016 (a selective inhibitor of 20-HETE synthesis) reduced cell viability by 49*-64%* (*p < 0...
August 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28635053/protective-effects-of-lepidium-meyenii-maca-aqueous-extract-and-lycopene-on-testosterone-propionate-induced-prostatic-hyperplasia-in-mice
#17
Ying Zou, Waleed Aboshora, Jing Li, Tiancun Xiao, Lianfu Zhang
The inhibitory effect of maca extractant, lycopene, and their combination was evaluated in benign prostatic hyperplasia (BPH) mice induced by testosterone propionate. Mice were divided into a saline group, solvent control group and testosterone propionate-induced BPH mice [BPH model group, solvent BPH model group, benzyl glucosinolate group (1.44 mg/kg), maca group (60 mg/kg), lycopene treated (15, 5, and 2.5 mg/kg), maca (30 mg/kg) combine lycopene treated (7.5, 2.5, and 1.25 mg/kg), and finasteride treated]...
June 20, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28624515/development-of-selective-androgen-receptor-modulators-sarms
#18
REVIEW
Ramesh Narayanan, Christopher C Coss, James T Dalton
The Androgen Receptor (AR), a member of the steroid hormone receptor family, plays important roles in the physiology and pathology of diverse tissues. AR ligands, which include circulating testosterone and locally synthesized dihydrotestosterone, bind to and activate the AR to elicit their effects. Ubiquitous expression of the AR, metabolism and cross reactivity with other receptors limit broad therapeutic utilization of steroidal androgens. However, the discovery of selective androgen receptor modulators (SARMs) and other tissue-selective nuclear hormone receptor modulators that activate their cognate receptors in a tissue-selective manner provides an opportunity to promote the beneficial effects of androgens and other hormones in target tissues with greatly reduced unwanted side-effects...
June 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28619249/metabolism-of-sex-steroids-is-influenced-by-acquired-adiposity-a-study-of-young-adult-male-monozygotic-twin-pairs
#19
Veera Vihma, Jussi Naukkarinen, Ursula Turpeinen, Esa Hämäläinen, Jaakko Kaprio, Aila Rissanen, Sini Heinonen, Antti Hakkarainen, Jesper Lundbom, Nina Lundbom, Tomi S Mikkola, Matti J Tikkanen, Kirsi H Pietiläinen
Obesity and ageing are associated with lower serum testosterone levels in men. How fat distribution or adipose tissue metabolism, independent of genetic factors and age, are related to sex steroid metabolism is less clear. We studied the associations between adiposity and serum sex hormone concentrations, and mRNA expression of genes regulating sex hormone metabolism in adipose tissue in young adult male monozygotic (MZ) twin pairs. The subjects [n=18 pairs; mean age, 32 years; individual body mass indexes (BMIs) 22-36kg/m(2)] included 9 male MZ twin pairs discordant for BMI [intra-pair difference (Δ) in BMI ≥3kg/m(2)]...
June 12, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28611094/agonist-specific-protein-interactomes-of-glucocorticoid-and-androgen-receptor-as-revealed-by-proximity-mapping
#20
Joanna K Lempiäinen, Einari A Niskanen, Kaisa-Mari Vuoti, Riikka E Lampinen, Helka Göös, Markku Varjosalo, Jorma J Palvimo
Glucocorticoid receptor (GR) and androgen receptor (AR) are steroid-inducible transcription factors (TFs). GR and AR are central regulators of various metabolic, homeostatic and differentiation processes and hence important therapeutic targets, especially in inflammation and prostate cancer, respectively. Hormone binding to these steroid receptors (SRs) leads to DNA binding and activation or repression of their target genes with the aid of interacting proteins, coregulators. However, protein interactomes of these important drug targets have remained poorly defined...
June 13, 2017: Molecular & Cellular Proteomics: MCP
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