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Androgen insensitivity

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https://www.readbyqxmd.com/read/29785970/phenotypic-and-molecular-characteristics-of-androgen-insensitivity-syndrome-patients
#1
Shi-Min Yuan, Ya-Nan Zhang, Juan Du, Wen Li, Chao-Feng Tu, Lan-Lan Meng, Ge Lin, Guang-Xiu Lu, Yue-Qiu Tan
Androgen insensitivity syndrome (AIS), an X-linked recessive genetic disorder of sex development, is caused by mutations in the androgen receptor (AR) gene, and is characterized by partial or complete inability of specific tissues to respond to androgens in individuals with the 46,XY karyotype. This study aimed to investigate AR gene mutations and to characterize genotype-phenotype correlations. Ten patients from unrelated families, aged 2-31 years, were recruited in the study. Based on karyotype, altered hormone profile, and clinical manifestations, nine patients were preliminarily diagnosed with complete AIS and one with partial AIS...
May 18, 2018: Asian Journal of Andrology
https://www.readbyqxmd.com/read/29783631/melatonin-analogue-antiproliferative-and-cytotoxic-effects-on-human-prostate-cancer-cells
#2
Angela Calastretti, Giuliana Gatti, Valeria Lucini, Silvana Dugnani, Gianfranco Canti, Francesco Scaglione, Annamaria Bevilacqua
Melatonin has been indicated as a possible oncostatic agent in different types of cancer, its antiproliferative role being demonstrated in several in vitro and in vivo experimental models of tumors. Specifically, melatonin was proven to inhibit cell growth of both androgen-dependent and independent prostate cancer cells, through various mechanisms. A number of melatonin derivatives have been developed and tested for their role in the prevention and treatment of neoplastic diseases. We recently proved the in vitro and in vivo anticancer activity of UCM 1037, a newly-synthetized melatonin analogue, on melanoma and breast cancer cells...
May 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29768628/androgen-insensitivity-syndrome-a-review
#3
Rafael Loch Batista, Elaine M Frade Costa, Andresa de Santi Rodrigues, Nathalia Lisboa Gomes, José Antonio Faria, Mirian Y Nishi, Ivo Jorge Prado Arnhold, Sorahia Domenice, Berenice Bilharinho de Mendonca
Androgenic insensitivity syndrome is the most common cause of disorders of sexual differentiation in 46,XY individuals. It results from alterations in the androgen receptor gene, leading to a frame of hormonal resistance, which may present clinically under 3 phenotypes: complete (CAIS), partial (PAIS) or mild (MAIS). The androgen receptor gene has 8 exons and 3 domains, and allelic variants in this gene occur in all domains and exons, regardless of phenotype, providing a poor genotype - phenotype correlation in this syndrome...
March 2018: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29707793/interleukin-6-induces-vegf-secretion-from-prostate-cancer-cells-in-a-manner-independent-of-androgen-receptor-activation
#4
Kenichiro Ishii, Takeshi Sasaki, Kazuhiro Iguchi, Shinya Kajiwara, Manabu Kato, Hideki Kanda, Yoshifumi Hirokawa, Kiminobu Arima, Atsushi Mizokami, Yoshiki Sugimura
BACKGROUND: The reduced androgen-sensitivity of prostate cancer (PCa) cells is an important clinical development because of its association with the cells' progression to castration-resistant prostate cancer (CRPC). During androgen deprivation therapy (ADT), stroma-derived growth factors and cytokines can activate the androgen receptor (AR). For example, IL-6 is a multifunctional cytokine that is involved in the malignancy of PCa cells through AR activation. In the present study, we used an androgen-sensitive human PCa cell line (LNCaP) and its sublines to investigate the relationship between the responsiveness of PCa cells to IL-6 treatment and the cellular AR signaling pathway...
April 29, 2018: Prostate
https://www.readbyqxmd.com/read/29707681/hershberger-assays-for-di-2-ethylhexyl-phthalate-and-its-substitute-candidates
#5
Hee-Su Kim, Yong-Pil Cheon, Sung-Ho Lee
In the present study, we employed Hershberger assay to determine possible androgenic or antiandrogenic activities of three di-2-ethylhexyl phthalate (DEHP) substitute candidates. The assay was carried out using immature castrated Sprague-Dawley male rats. After 7 days of the surgery, testosterone propionate (TP, 0.4 mg/kg/day) and test materials (low dose, 40 mg/kg/day; high dose, 400 mg/kg/day) were administered for 10 consecutive days by subcutaneous (s.c.) injection and oral gavage, respectively. Test materials were DEHP, 2-ethylhexyl oleate (IOO), 2-ethylhexyl stearate (IOS) and triethyl 2-acetylcitrate (ATEC)...
March 2018: Balsaeng'gwa Saengsig
https://www.readbyqxmd.com/read/29684818/glut1-protects-prostate-cancer-cells-from-glucose-deprivation-induced-oxidative-stress
#6
Pedro Gonzalez-Menendez, David Hevia, Rebeca Alonso-Arias, Alejandro Alvarez-Artime, Aida Rodriguez-Garcia, Sandrina Kinet, Ivan Gonzalez-Pola, Naomi Taylor, Juan C Mayo, Rosa M Sainz
Glucose, chief metabolic support for cancer cell survival and growth, is mainly imported into cells by facilitated glucose transporters (GLUTs). The increase in glucose uptake along with tumor progression is due to an increment of facilitative glucose transporters as GLUT1. GLUT1 prevents cell death of cancer cells caused by growth factors deprivation, but there is scarce information about its role on the damage caused by glucose deprivation, which usually occurs within the core of a growing tumor. In prostate cancer (PCa), GLUT1 is found in the most aggressive tumors, and it is regulated by androgens...
April 12, 2018: Redox Biology
https://www.readbyqxmd.com/read/29615040/multicentre-cross-sectional-clinical-evaluation-study-about-quality-of-life-in-adults-with-disorders-differences-of-sex-development-dsd-compared-to-country-specific-reference-populations-dsd-life
#7
Marion Rapp, Esther Mueller-Godeffroy, Peter Lee, Robert Roehle, Baudewijntje P C Kreukels, Birgit Köhler, Anna Nordenström, Claire Bouvattier, Ute Thyen
BACKGROUND: Previous studies in quality of life (QOL) in individuals with disorders/differences of sex development (DSD) have been restricted to subpopulations of the condition. We describe QOL in adult persons with DSD compared to country specific references and assess the impact of diagnosis. METHODS: The multicentre cross-sectional clinical evaluation (dsd-LIFE) took place in 14 specialized clinics in six European countries. Adolescents (≥16 years) and adults having a DSD condition were included from 02/2014 to 09/2015...
April 3, 2018: Health and Quality of Life Outcomes
https://www.readbyqxmd.com/read/29599322/crosstalk-between-androgen-sensitive-and-androgen-insensitive-prostate-cancer-cells
#8
Yuta Takezawa, Kouji Izumi, Kazuaki Machioka, Hiroaki Iwamoto, Renato Naito, Tomoyuki Makino, Suguru Kadomoto, Ariunbold Natsagdorj, Yoshifumi Kadono, Evan T Keller, Jian Zhang, Atsushi Mizokami
AIM: To investigate how androgen-sensitive LNCaP cells crosstalk with androgen-insensitive DU145 or PC-3 cells. MATERIALS AND METHODS: The numbers of LNCaP cells were counted when co-cultured with DU145 or PC-3 cells and vise versa. Androgen receptor (AR) activity in LNCaP cells was examined by luciferase reporter assay after transfection with a luciferase reporter driven by PSA promoter in the presence of DU145 or PC-3 cells. Concentration of androgens in the medium was measured by liquid chromatography-mass spectrometry (LC-MS/MS)...
April 2018: Anticancer Research
https://www.readbyqxmd.com/read/29555975/orphan-nuclear-receptor-tlx-contributes-to-androgen-insensitivity-in-castration-resistant-prostate-cancer-via-its-repression-of-androgen-receptor-transcription
#9
Lin Jia, Dinglan Wu, Yuliang Wang, Wenxing You, Zhu Wang, Lijia Xiao, Ganhui Cai, Zhenyu Xu, Chang Zou, Fei Wang, Jeremy Yuen-Chun Teoh, Chi-Fai Ng, Shan Yu, Franky L Chan
The metastatic castration-resistant prostate cancer (CRPC) is a lethal form of prostate cancer, in which the expression of androgen receptor (AR) is highly heterogeneous. Indeed, lower AR expression and attenuated AR signature activity is shown in CRPC tissues, especially in the subset of neuroendocrine prostate cancer (NEPC) and prostate cancer stem-like cells (PCSCs). However, the significance of AR downregulation in androgen insensitivity and de-differentiation of tumor cells in CRPC is poorly understood and much neglected...
March 20, 2018: Oncogene
https://www.readbyqxmd.com/read/29524555/elevated-phospholipase-d-activity-in-androgen-insensitive-prostate-cancer-cells-promotes-both-survival-and-metastatic-phenotypes
#10
Matthew Utter, Sohag Chakraborty, Limor Goren, Lucas Feuser, Yuan-Shan Zhu, David A Foster
Prostate cells are hormonally driven to grow and divide. Typical treatments for prostate cancer involve blocking activation of the androgen receptor by androgens. Androgen deprivation therapy can lead to the selection of cancer cells that grow and divide independently of androgen receptor activation. Prostate cancer cells that are insensitive to androgens commonly display metastatic phenotypes and reduced long-term survival of patients. In this study we provide evidence that androgen-insensitive prostate cancer cells have elevated PLD activity relative to the androgen-sensitive prostate cancer cells...
June 1, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29464380/the-metabolic-and-endocrine-characteristics-in-spinal-and-bulbar-muscular-atrophy
#11
Angela Rosenbohm, Susanne Hirsch, Alexander E Volk, Torsten Grehl, Julian Grosskreutz, Frank Hanisch, Andreas Herrmann, Katja Kollewe, Wolfram Kress, Thomas Meyer, Susanne Petri, Johannes Prudlo, Carsten Wessig, Hans-Peter Müller, Jens Dreyhaupt, Jochen Weishaupt, Christian Kubisch, Jan Kassubek, Patrick Weydt, Albert C Ludolph
OBJECTIVE: Spinal and bulbar muscular atrophy (SBMA) is caused by an abnormal expansion of the CAG repeat in the androgen receptor gene. This study aimed to systematically phenotype a German SBMA cohort (n = 80) based on laboratory markers for neuromuscular, metabolic, and endocrine status, and thus provide a basis for the selection of biomarkers for future therapeutic trials. METHODS: We assessed a panel of 28 laboratory parameters. The clinical course and blood biomarkers were correlated with disease duration and CAG repeat length...
May 2018: Journal of Neurology
https://www.readbyqxmd.com/read/29398092/prenatal-testosterone-and-theory-of-mind-development-findings-from-disorders-of-sex-development
#12
Behzad S Khorashad, Behnaz Khazai, Ghasem M Roshan, Mehran Hiradfar, Mozhgan Afkhamizadeh, Tim C van de Grift
Women on average perform better than men on the "Reading the Mind in the Eyes" test (RMET) which is a measure of Theory of Mind (ToM). The aim of this study was to assess whether these sex differences are influenced by differences in prenatal testosterone levels through a study on individuals with Disorders of Sex Development and matched controls. ToM performance was examined using the RMET in female-assigned-at-birth individuals with increased prenatal testosterone exposure (Congenital Adrenal Hyperplasia (CAH) and 5-alpha Reductase type-2 Deficiency (5α-RD-2)), female-assigned-at-birth individuals with testosterone insensitivity (Complete Androgen Insensitivity Syndrome (CAIS)), and their age-matched unaffected male and female relatives...
March 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29396419/partial-androgen-insensitivity-syndrome-caused-by-a-deep-intronic-mutation-creating-an-alternative-splice-acceptor-site-of-the-ar-gene
#13
Hiroyuki Ono, Hirotomo Saitsu, Reiko Horikawa, Shinichi Nakashima, Yumiko Ohkubo, Kumiko Yanagi, Kazuhiko Nakabayashi, Maki Fukami, Yasuko Fujisawa, Tsutomu Ogata
Although partial androgen insensitivity syndrome (PAIS) is caused by attenuated responsiveness to androgens, androgen receptor gene (AR) mutations on the coding regions and their splice sites have been identified only in <25% of patients with a diagnosis of PAIS. We performed extensive molecular studies including whole exome sequencing in a Japanese family with PAIS, identifying a deep intronic variant beyond the branch site at intron 6 of AR (NM_000044.4:c.2450-42 G > A). This variant created the splice acceptor motif that was accompanied by pyrimidine-rich sequence and two candidate branch sites...
February 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29393262/androgen-insensitivity-syndrome-at-prepuberty-marked-loss-of-spermatogonial-cells-at-early-childhood-and-presence-of-gonocytes-up-to-puberty
#14
Paula Aliberti, Natalia Perez Garrido, Roxana Marino, Pablo Ramirez, Alberto J Solari, Roberta Sciurano, Mariana Costanzo, Gabriela Guercio, Diana Mónica Warman, Marcela Bailez, María Sonia Baquedano, Marco A Rivarola, Alicia Belgorosky, Esperanza Berensztein
Androgen insensitivity syndrome (AIS) is a hereditary condition in patients with a 46,XY karyotype in which loss-of-function mutations of the androgen receptor (AR) gene are responsible for defects in virilization. The aim of this study was to investigate the consequences of the lack of AR activity on germ cell survival and the degree of testicular development reached by these patients by analyzing gonadal tissue from patients with AIS prior to Sertoli cell maturation at puberty. Twenty-three gonads from 13 patients with AIS were assessed and compared to 18 testes from 17 subjects without endocrine disorders...
2017: Sexual Development: Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation
https://www.readbyqxmd.com/read/29388223/aberrant-breast-tissue-in-complete-androgen-insensitivity-syndrome
#15
G Nazzaro, G Genovese, M Brena, E Passoni, G Tadini
No abstract text is available yet for this article.
February 1, 2018: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/29386228/disorders-of-sex-development-a-study-of-194-cases
#16
R Walia, M Singla, K Vaiphei, S Kumar, A Bhansali
OBJECTIVE: To study the clinical profile and the management of patients with disorders of sex development (DSD). DESIGN AND SETTING: Retrospective study from a tertiary care hospital of North India. METHODS AND PATIENTS: One hundred ninety-four patients of DSD registered in the Endocrine clinic of Postgraduate Institute of Medical Education and Research, Chandigarh between 1995 and 2014 were included. RESULTS: One hundred and two patients (52...
February 2018: Endocrine Connections
https://www.readbyqxmd.com/read/29375715/dietary-flavonoid-tangeretin-induces-reprogramming-of-epithelial-to-mesenchymal-transition-in-prostate-cancer-cells-by-targeting-the-pi3k-akt-mtor-signaling-pathway
#17
Wen-Bin Zhu, Ning Xiao, Xing-Jie Liu
Tangeretin, a natural polymethoxyflavone present in the peel of citrus fruits is known to exhibit anticancer properties against a variety of carcinomas. Previous experimental evidence suggests that lifestyle and dietary habits affect the risk of prostate cancer to a certain extent. As the effect of tangeretin on prostate cancer is unexplored, the present study investigated the effect of tangeretin on androgen-insensitive PC-3 cells and androgen-sensitive LNCaP cells. Tangeretin reduced the cell viability of PC-3 cells in a dose- and time-dependent manner, with the half-maximal inhibitory concentration (IC50 ) observed at 75 µM dose following 72 h of incubation, while in LNCaP cells, the IC50 was identified to be ~65 µM...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29370587/-the-impact-of-the-androgen-receptor-splice-variant-ar-v7-on-the-prognosis-and-treatment-of-advanced-prostate-cancer
#18
P Thelen, H Taubert, S Duensing, G Kristiansen, A S Merseburger, M V Cronauer
A recently discovered mechanism enabling prostate cancer cells to escape the effects of endocrine therapies consists in the synthesis of C-terminally truncated, constitutively active androgen receptor (AR) splice variants (AR-V). Devoid of a functional C-terminal hormone/ligand binding domain, various AR-Vs are insensitive to therapies targeting the androgen/AR signalling axis. Preliminary studies suggest that AR-V7, the most common AR-V, is a promising predictive tumour marker and a relevant selection marker for the treatment of advanced prostate cancer...
January 25, 2018: Aktuelle Urologie
https://www.readbyqxmd.com/read/29354789/hershberger-assays-for-bisphenol-a-and-its-substitute-candidates
#19
Hee-Su Kim, Yong-Bin Kim, Donchan Choi, Yong-Pil Cheon, Sung-Ho Lee
Bisphenol-A(BPA) is a member of alkylphenol family, and shows adverse effects including reduced fertility, reproductive tract abnormalities, metabolic disorder, cancer induction, neurotoxicity and immunotoxicity. In the present study, we conducted Hershberger assay to evaluate whether the two candidates to replace BPA have androgenic or antiandrogenic activity. The assay was carried out using immature castrated Sprague-Dawley male rats. After 7 days of the surgery, testosterone propionate (TP, 0.4 mg/kg/day) and test materials (low dose, 40 mg/kg/day; high dose, 400 mg/kg/day) were administered for 10 consecutive days by subcutaneous (s...
December 2017: Balsaeng'gwa Saengsig
https://www.readbyqxmd.com/read/29306929/comparison-between-two-inhibin-b-elisa-assays-in-46-xy-testicular-disorders-of-sex-development-dsd-with-normal-testosterone-secretion
#20
Guilherme Guaragna-Filho, Antônio Ramos Calixto, Georgette Beatriz De Paula, Laurione Cândido De Oliveira, André Moreno Morcillo, Maricilda Palandi De Mello, Andrea Trevas Maciel-Guerra, Gil Guerra-Junior
BACKGROUND: Inhibin B is a hormone produced by the Sertoli cells that can provide important information for the investigation of disorders of sex development (DSD) with 46,XY karyotype. The aim of this study is to compare two enzyme-linked immunosorbent assay (ELISA) assays for dosage of serum inhibin B in patients with 46,XY DSD with normal testosterone secretion. METHODS: Twenty-nine patients with 46,XY DSD and normal testosterone secretion (partial androgen insensitivity syndrome [PAIS] [n=8]; 5α-reductase deficiency [n=7] and idiopathic 46,XY DSD [n=14]) were included...
January 26, 2018: Journal of Pediatric Endocrinology & Metabolism: JPEM
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