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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
#1
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
#2
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
#3
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
#4
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
#5
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/28261839/clinical-and-molecular-characteristics-in-15-patients-with-androgen-receptor-gene-mutations-from-south-china
#6
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/28247927/osteogenesis-and-mineralization-of-mesenchymal-stem-cells-in-collagen-type-i-based-recombinant-peptide-scaffolds
#7
Kendell M Pawelec, Davide Confalonieri, Franziska Ehlicke, Huibert A van Boxtel, Heike Walles, Sebastiaan G J M Kluijtmans
Recombinant peptides have the power to harness the inherent biocompatibility of natural macro-molecules, while maintaining a defined chemistry for use in tissue engineering. Creating scaffolds from peptides requires stabilization via cross-linking, a process known to alter both mechanics and density of adhesion ligands. The chemistry and mechanics of linear scaffolds from a recombinant peptide based on human collagen type I (RCP) was investigated after cross-linking. Three treatments were compared: dehydrothermal treatment (DHT), hexamethylene diisocyanate (HMDIC), and genipin...
March 1, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28241109/sex-steroid-hormones-in-relation-to-barrett-s-esophagus-an-analysis-of-the-finbar-study
#8
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/28235766/sigma1-targeting-to-suppress-aberrant-androgen-receptor-signaling-in-prostate-cancer
#9
Jeffrey D Thomas, Charles G Longen, Halley M Oyer, Nan Chen, Christina M Maher, Joseph M Salvino, Blase Kania, Kelsey N Anderson, William F Ostrander, Karen E Knudsen, Felix J Kim
Suppression of androgen receptor (AR) activity in prostate cancer by androgen depletion or direct AR antagonist treatment, although initially effective, leads to incurable castration resistant prostate cancer (CRPC) via compensatory mechanisms including resurgence of AR and AR splice variant (ARV) signaling. Emerging evidence suggests that Sigma1 (also known as sigma-1 receptor) is a unique chaperone or scaffolding protein that contributes to cellular protein homeostasis. We reported previously that some Sigma1-selective small molecules can be used to pharmacologically modulate protein homeostasis pathways...
February 24, 2017: Cancer Research
https://www.readbyqxmd.com/read/28223151/testosterone-rapidly-increases-ca-2-activated-k-currents-causing-hyperpolarization-in-human-coronary-artery-endothelial-cells
#10
Katesirin Ruamyod, Wattana B Watanapa, Chairat Shayakul
Testosterone has endothelium-dependent vasodilatory effects on the coronary artery, with some reports suggesting endothelial ion channel involvement. This study employed the whole-cell patch clamp technique to investigate the effect of testosterone on ion channels in human coronary artery endothelial cells (HCAECs) and the mechanisms involved. We found that 0.03-3μM testosterone significantly induced a rapid, concentration-dependent increase in total HCAEC current (EC50, 71.96±1.66nM; maximum increase, 59...
February 20, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28216900/trichosanthes-kirilowii-exerts-androgenic-activity-via-regulation-of-psa-and-klk2-in-22rv1-prostate-cancer-cells
#11
Soo-Jin Jeong, Ji-Yoon Choi, Mi-Sook Dong, Chang-Seob Seo, Hyeun-Kyoo Shin
BACKGROUND: The androgen comprises a group of hormones that play roles in male reproductive activity as well as personal characteristics. OBJECTIVE: We investigated the androgenic activity of various herbal medicines in human prostate cancer 22Rv1 cells. MATERIALS AND METHODS: Herbal extracts of Trichosanthes kirilowii (TK), Asarum sieboldii (AS), Sanguisorba officinalis (SO), and Xanthium strumarium (XS) were selected to have androgenic effects based on a preliminary in vitro screening system...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28216616/cd8-t-cells-promote-proliferation-of-benign-prostatic-hyperplasia-epithelial-cells-under-low-androgen-level-via-modulation-of-ccl5-stat5-ccnd1-signaling-pathway
#12
Yang Yang, Shuai Hu, Jie Liu, Yun Cui, Yu Fan, Tianjing Lv, Libo Liu, Jun Li, Qun He, Wenke Han, Wei Yu, Yin Sun, Jie Jin
Previous studies by our group have shown that low intra-prostatic dihydrotestosterone (DHT) induced BPH epithelial cells (BECs) to recruit CD8+ T cells. However, the influence of the recruited CD8+ T cells on BECs under a low androgen level is still unknown. Here, we found CD8+ T cells have the capacity to promote proliferation of BECs in low androgen condition. Mechanism dissection revealed that interaction between CD8+ T cells and BECs through secretion of CCL5 might promote the phosphorylation of STAT5 and a higher expression of CCND1 in BECs...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28213978/estrogens-and-androgens-inhibit-association-of-rankl-with-the-pre-osteoblast-membrane-through-post-translational-mechanisms
#13
Anthony Martin, Jiali Yu, Jian Xiong, Aysha B Khalid, Benita Katzenellenbogen, Sung Hoon Kim, John A Katzenellenbogen, Suchinda Malaivijitnond, Yankel Gabet, Susan A Krum, Baruch Frenkel
We have recently demonstrated that RUNX2 promoted, and 17-β-Estradiol (E2) diminished, association of RANKL with the cell membrane in pre-osteoblast cultures. Here we show that, similar to E2, dihydrotestosterone (DHT) diminishes association of RANKL and transiently transfected GFP-RANKL with the pre-osteoblast membrane without decreasing total RANKL mRNA or protein levels. Diminution of membrane-associated RANKL was accompanied with marked suppression of osteoclast differentiation from co-cultured pre-osteoclasts, even though DHT increased, not decreased, RANKL concentrations in pre-osteoblast conditioned media...
February 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28194662/mmtv-pymt-and-derived-met-1-mouse-mammary-tumor-cells-as-models-for-studying-the-role-of-the-androgen-receptor-in-triple-negative-breast-cancer-progression
#14
Jessica L Christenson, Kiel T Butterfield, Nicole S Spoelstra, John D Norris, Jatinder S Josan, Julie A Pollock, Donald P McDonnell, Benita S Katzenellenbogen, John A Katzenellenbogen, Jennifer K Richer
Triple-negative breast cancer (TNBC) has a faster rate of metastasis compared to other breast cancer subtypes, and no effective targeted therapies are currently FDA-approved. Recent data indicate that the androgen receptor (AR) promotes tumor survival and may serve as a potential therapeutic target in TNBC. Studies of AR in disease progression and the systemic effects of anti-androgens have been hindered by the lack of an AR-positive (AR+) immunocompetent preclinical model. In this study, we identified the transgenic MMTV-PyMT (mouse mammary tumor virus-polyoma middle tumor-antigen) mouse mammary gland carcinoma model of breast cancer and Met-1 cells derived from this model as tools to study the role of AR in breast cancer progression...
February 13, 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28182747/investigation-of-the-in-vitro-and-in-vivo-efficiency-of-rm-532-105-a-17%C3%AE-hydroxysteroid-dehydrogenase-type-3-inhibitor-in-lapc-4-prostate-cancer-cell-and-tumor-models
#15
Lucie Carolle Kenmogne, Jenny Roy, René Maltais, Mélanie Rouleau, Bertrand Neveu, Frédéric Pouliot, Donald Poirier
In the fight against androgen-sensitive prostate cancer, the enzyme 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) is an attractive therapeutic target considering its key role in the formation of androgenic steroids. In this study, we attempted to assess the in vivo efficacy of the compound RM-532-105, an androsterone derivative developed as an inhibitor of 17β-HSD3, in the prostate cancer model of androgen-sensitive LAPC-4 cells xenografted in nude mice. RM-532-105 did not inhibit the tumor growth induced by 4-androstene-3,17-dione (4-dione); rather, the levels of the androgens testosterone (T) and dihydrotestosterone (DHT) increased within the tumors...
2017: PloS One
https://www.readbyqxmd.com/read/28176462/hormonal-treatment-ffects-on-the-cross-sectional-area-of-pubococcygeus-muscle-fibers-after-denervation-and-castration-in-male-rats
#16
Miguel Lara-García, Mayvi Alvarado, Estela Cuevas, Omar Lara-Garcia, Dale R Sengelaub, Pablo Pacheco
We explore the interaction of muscle innervation and gonadal hormone action in the pubococcygeus muscle (Pcm) after castration and hormone replacement. Male Wistar rats were castrated and the Pcm was unilaterally denervated; after 2 or 6 weeks, the cross-sectional area (CSA) of Pcm fibers was assessed. Additional groups of castrated rats were used to examine the effects of hormone replacement. At 2 weeks post surgeries, rats were implanted with Silastic capsules containing either dihydrotestosterone (DHT), estradiol benzoate (EB) or both hormones, and the CSA of Pcm fibers was assessed after 4 weeks of hormone treatment...
February 8, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/28157253/total-testosterone-to-dihydrotestosterone-ratio-assessed-by-lc-ms-ms-predicts-a-worse-metabolic-profile-not-only-in-pcos-patients
#17
Urszula Ambroziak, Alina Kuryłowicz, Anna Kępczyńska-Nyk, Zbigniew Bartoszewicz, Agnieszka Kondracka, Radosław Jaźwiec, Emilia Samborowska, Michał Dadlez, Aleksandra Wysłouch-Cieszyńska, Tomasz Bednarczuk
OBJECTIVES: Total testosterone/dihydrotestosterone ratio (TT/DHT) was found to determine metabolic risk in polycystic ovary syndrome (PCOS). The aim of this study was to analyze whether (TT/DHT) may be helpful in predicting metabolic risk not only in PCOS patients but also in healthy women. MATERIAL AND METHODS: Total testosterone (TT), dihydrotestosterone (DHT), androstendione and dehydroepiandrosterone sulphate (DHEA-S) were measured by LC-MS/MS in 36 women with PCOS and in 29 age-matched controls without clinical hyperandrogenism...
2017: Ginekologia Polska
https://www.readbyqxmd.com/read/28145028/effects-of-steroidal-antiandrogen-or-5-alpha-reductase-inhibitor-on-prostate-tissue-hormone-content
#18
Yasuhiro Shibata, Seiji Arai, Yoshiyuki Miyazawa, Takahiro Shuto, Masashi Nomura, Yoshitaka Sekine, Hidekazu Koike, Hiroshi Matsui, Kazuto Ito, Kazuhiro Suzuki
BACKGROUND: The effects of a steroidal antiandrogen (AA) and 5-alpha-reductase inhibitor (5ARI) on prostate tissue hormone content and metabolism are not fully elucidated. The objective of this study is to investigate the hormone content and metabolism of the prostate tissues of patients treated with AA or 5ARI using the ultra-sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. METHODS: Thirty-nine patients with benign prostatic hyperplasia (BPH) undergoing transurethral surgery were included...
February 1, 2017: Prostate
https://www.readbyqxmd.com/read/28130740/effect-of-male-house-mouse-pheromone-components-on-behavioral-responses-of-mice-in-laboratory-and-field-experiments
#19
Antonia E Musso, Regine Gries, Huimin Zhai, Stephen Takács, Gerhard Gries
Urine of male house mice, Mus musculus, is known to have primer pheromone effects on the reproductive physiology of female mice. Urine-mediated releaser pheromone effects that trigger certain behavioral responses are much less understood, and no field studies have investigated whether urine deposits by male or female mice, or synthetic mouse pheromone, increase trap captures of mice. In field experiments, we baited traps with bedding soiled with urine and feces of caged female or male mice, and recorded captures of mice in these and in control traps containing clean bedding...
January 27, 2017: Journal of Chemical Ecology
https://www.readbyqxmd.com/read/28120456/endothelin-1-mediates-natriuresis-but-not-polyuria-during-vitamin-d-induced-acute-hypercalcemia
#20
Natsuko Tokonami, Lydie Cheval, Isabelle Monnay, Guillaume Meurice, Johaness Loffing, Eric Feraille, Pascal Houillier
Acute hypercalcemia increases urinary sodium and water excretion; however, the underlying molecular mechanism remains unclear. As vitamin D-induced hypercalcemia increases the renal expression of endothelin (ET)-1, we hypothesized that ET-1 mediates the effects of hypercalcemia on renal sodium and water handling. Hypercalcemia was induced in 8 week-old, PTH-supplemented, male mice by oral administration of dihydrotachysterol (DHT) for 3 days. DHT-treated mice became hypercalcemic and displayed increased urinary water and sodium excretion compared to controls...
January 24, 2017: Journal of Physiology
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