2018 EAU Male Hypogonadism Search Strategy
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Blueprint Genetics ANOS1 Single Gene Test
ANOS1 single gene test Test code: S00125 Phenotype information Kallmann syndrome Alternative gene names KALIG-1, WFDC19 Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more. Panels that include the ANOS1 gene Kallmann Syndrome Panel Abnormal Genitalia/ Disorders of Sex Development Panel Test Strengths The strengths of this test include: CAP accredited laboratory CLIA-certified personnel performing clinical testing in a CLIA-certified laboratory Powerful sequencing technologies, advanced target enrichment methods and precision bioinformatics pipelines ensure superior analytical performance Careful construction of clinically effective and scientifically justified gene panels Our Nucleus online portal providing transparent and easy access to quality and performance data at the patient level Our publicly available analytic validation demonstrating complete details of test performance ~2,000 non-coding disease causing variants in our clinical grade NGS assay for panels (please see ‘Non-coding disease causing variants covered by this test’) Our rigorous variant classification scheme Our systematic clinical interpretation workflow using proprietary software enabling accurate and traceable processing of NGS data Our comprehensive clinical statements Test Limitations This test does not detect the following: Complex inversions Gene conversions -
Sex Hormones Related Ocular Dryness in Breast Cancer Women
Journal of Clinical Medicine Review Sex Hormones Related Ocular Dryness in Breast Cancer Women Antonella Grasso 1, Antonio Di Zazzo 2,* , Giuseppe Giannaccare 3 , Jaemyoung Sung 4 , Takenori Inomata 4 , Kendrick Co Shih 5 , Alessandra Micera 6, Daniele Gaudenzi 2, Sara Spelta 2 , Maria Angela Romeo 7, Paolo Orsaria 1, Marco Coassin 2 and Vittorio Altomare 1 1 Breast Unit, University Campus Bio-Medico, 00128 Rome, Italy; [email protected] (A.G.); [email protected] (P.O.); [email protected] (V.A.) 2 Ophthalmology Operative Complex Unit, University Campus Bio-Medico, 00128 Rome, Italy; [email protected] (D.G.); [email protected] (S.S.); [email protected] (M.C.) 3 Department of Ophthalmology, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; [email protected] 4 Department of Ophthalmology, School of Medicine, Juntendo University, 1130033 Tokyo, Japan; [email protected] (J.S.); [email protected] (T.I.) 5 Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong; [email protected] 6 Research and Development Laboratory for Biochemical, Molecular and Cellular Applications in Ophthalmological Sciences, IRCCS–Fondazione Bietti, 00198 Rome, Italy; [email protected] 7 School of Medicine, Humanitas University, 20089 Milan, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-06225418893; Fax: +39-9622541456 Abstract: Background: Dry eye syndrome (DES) is strictly connected to systemic and topical sex hor- mones. Breast cancer treatment, the subsequent hormonal therapy, the subsequent hyperandrogenism and the early sudden menopause, may be responsible for ocular surface system failure and its clinical Citation: Grasso, A.; Di Zazzo, A.; manifestation as dry eye disease. -
Kisspeptin and Testicular Function—Is It Necessary?
International Journal of Molecular Sciences Review Kisspeptin and Testicular Function—Is It Necessary? Aditi Sharma 1 , Thilipan Thaventhiran 1, Suks Minhas 2, Waljit S. Dhillo 1 and Channa N. Jayasena 1,* 1 Section of Investigative Medicine, Imperial College, 6th Floor, Commonwealth Building, Hammersmith Hospital, 150 Du Cane Road, London W12 0NN, UK; [email protected] (A.S.); [email protected] (T.T.); [email protected] (W.S.D.) 2 Department of Urology, Imperial College Healthcare NHS Trust, Charing Cross Hospital, Fulham Palace Road, Hammersmith, London W6 8RF, UK; [email protected] * Correspondence: [email protected] Received: 12 March 2020; Accepted: 21 April 2020; Published: 22 April 2020 Abstract: The role of kisspeptin in stimulating hypothalamic GnRH is undisputed. However, the role of kisspeptin signaling in testicular function is less clear. The testes are essential for male reproduction through their functions of spermatogenesis and steroidogenesis. Our review focused on the current literature investigating the distribution, regulation and effects of kisspeptin and its receptor (KISS1/KISS1R) within the testes of species studied to date. There is substantial evidence of localised KISS1/KISS1R expression and peptide distribution in the testes. However, variability is observed in the testicular cell types expressing KISS1/KISS1R. Evidence is presented for modulation of steroidogenesis and sperm function by kisspeptin signaling. However, the physiological importance of such effects, and whether these are paracrine or endocrine manifestations, remain unclear. Keywords: kisspeptin; kisspeptin receptor; spermatozoa; Leydig cells; Sertoli cells; testes; testosterone; LH; FSH; spermatogenesis 1. Introduction Kisspeptin is an established regulator of puberty onset [1,2], sexual maturation and adult reproductive activity [3]. -
Comparative Pharmacokinetic Study of Luteolin After Oral Administration Of
Vol. 8(16), pp. 422-428, 29 April, 2014 DOI 10.5897/AJPP2013.3835 ISSN 1996-0816 African Journal of Pharmacy and Copyright © 2014 Author(s) retain the copyright of this article Pharmacology http://www.academicjournals.org/AJPP Full Length Research Paper Comparative pharmacokinetic study of luteolin after oral administration of Chinese herb compound prescription JiMaiTong in spontaneous hypertensive rats (SHR) and Sprague Dawley (SD) rats Zhao-Huan Lou1, Su-Hong Chen2, Gui-Yuan Lv1*,Bo-Hou Xia1, Mei-Qiu Yan1, Zhi-Ru Zhang1 and Jian-Li Gao1 1Institute of Material Medica, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, China. 2Academy of Tradition Chinese Medicine, Wenzhou Medical University, Wenzhou 325035, China. Received 7 August, 2013; Accepted 15 April, 2014 JiMaiTong (JMT), a Chinese herb compound prescription consisted of Flos chrysanthemi Indici, Spica prunellae and Semen cassiae for anti-hypertension. Luteolin is one of the major bioactivity compositions in F. chrysanthemi Indici in JMT. There are some reports about pharmacokinetics of luteolin in extract of F. chrysanthemi and husks of peanut in normal rats, but it lacked pharmacokinetic information of luteolin residing in a Chinese herb compound prescription in hypertensive animal models. The present study aimed to develop a high-performance liquid chromatography with photodiode array detection (HPLC-DAD) method for determination of luteolin in rat plasma and for pharmacokinetic study after oral administration of JMT to spontaneous hypertensive rats (SHR) and normal Sprague Dawley (SD) rats. After oral administration of JMT to SHR and SD rats, respectively the content of luteolin in blood samples at different time points were determined by a reversed-phase high- performance liquid chromatography (RP-HPLC) coupled with liquid-liquid phase extraction. -
Novel Mutations in ANOS1 and FGFR1 Genes Agnieszka Gach1* , Iwona Pinkier1, Maria Szarras-Czapnik2, Agata Sakowicz3 and Lucjusz Jakubowski1
Gach et al. Reproductive Biology and Endocrinology (2020) 18:8 https://doi.org/10.1186/s12958-020-0568-6 RESEARCH Open Access Expanding the mutational spectrum of monogenic hypogonadotropic hypogonadism: novel mutations in ANOS1 and FGFR1 genes Agnieszka Gach1* , Iwona Pinkier1, Maria Szarras-Czapnik2, Agata Sakowicz3 and Lucjusz Jakubowski1 Abstract Background: Congenital hypogonadotropic hypogonadism (CHH) is a rare disease, triggered by defective GnRH secretion, that is usually diagnosed in late adolescence or early adulthood due to the lack of spontaneous pubertal development. To date more than 30 genes have been associated with CHH pathogenesis with X-linked recessive, autosomal dominant, autosomal recessive and oligogenic modes of inheritance. Defective sense of smell is present in about 50–60% of CHH patients and called Kallmann syndrome (KS), in contrast to patients with normal sense of smell referred to as normosmic CHH. ANOS1 and FGFR1 genes are all well established in the pathogenesis of CHH and have been extensively studied in many reported cohorts. Due to rarity and heterogenicity of the condition the mutational spectrum, even in classical CHH genes, have yet to be fully characterized. Methods: To address this issue we screened for ANOS1 and FGFR1 variants in a cohort of 47 unrelated CHH subjects using targeted panel sequencing. All potentially pathogenic variants have been validated with Sanger sequencing. Results: Sequencing revealed two ANOS1 and four FGFR1 mutations in six subjects, of which five are novel and one had been previously reported in CHH. Novel variants include a single base pair deletion c.313delT in exon 3 of ANOS1, three missense variants of FGFR1 predicted to result in the single amino acid substitutions c.331C > T (p.R111C), c.1964 T > C (p.L655P) and c.2167G > A (p.E723K) and a 15 bp deletion c.374_388delTGCCCGCAGACTCCG in exon 4 of FGFR1. -
Antidepressant-Like Behavioral and Neurochemical Effects of the Citrus
Available online at www.sciencedirect.com Life Sciences 82 (2008) 741–751 www.elsevier.com/locate/lifescie Antidepressant-like behavioral and neurochemical effects of the citrus-associated chemical apigenin ⁎ Li-Tao Yi, Jian-Mei Li, Yu-Cheng Li, Ying Pan, Qun Xu, Ling-Dong Kong State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, PR China Received 14 July 2007; accepted 16 January 2008 Abstract Apigenin is one type of bioflavonoid widely found in citrus fruits, which possesses a variety of pharmacological actions on the central nervous system. A previous study showed that acute intraperitoneal administration of apigenin had antidepressant-like effects in the forced swimming test (FST) in ddY mice. To better understand its pharmacological activity, we investigated the behavioral effects of chronic oral apigenin treatment in the FST in male ICR mice and male Wistar rats exposed to chronic mild stress (CMS). The effects of apigenin on central monoaminergic neurotransmitter systems, the hypothalamic–pituitary–adrenal (HPA) axis and platelet adenylyl cyclase activity were simultaneously examined in the CMS rats. Apigenin reduced immobility time in the mouse FST and reversed CMS-induced decrease in sucrose intake of rats. Apigenin also attenuated CMS-induced alterations in serotonin (5-HT), its metabolite 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA) levels and 5-HIAA/ 5-HT ratio in distinct rat brain regions. Moreover, apigenin reversed CMS-induced elevation in serum corticosterone concentrations and reduction in platelet adenylyl cyclase activity in rats. These results suggest that the antidepressant-like actions of oral apigenin treatment could be related to a combination of multiple biochemical effects, and might help to elucidate its mechanisms of action that are involved in normalization of stress- induced changes in brain monoamine levels, the HPA axis, and the platelet adenylyl cyclase activity. -
Diverse Pathomechanisms Leading to the Breakdown of Cellular Estrogen Surveillance and Breast Cancer Development: New Therapeutic Strategies
Journal name: Drug Design, Development and Therapy Article Designation: Review Year: 2014 Volume: 8 Drug Design, Development and Therapy Dovepress Running head verso: Suba Running head recto: Diverse pathomechanisms leading to breast cancer development open access to scientific and medical research DOI: http://dx.doi.org/10.2147/DDDT.S70570 Open Access Full Text Article REVIEW Diverse pathomechanisms leading to the breakdown of cellular estrogen surveillance and breast cancer development: new therapeutic strategies Zsuzsanna Suba Abstract: Recognition of the two main pathologic mechanisms equally leading to breast cancer National Institute of Oncology, development may provide explanations for the apparently controversial results obtained by sexual Budapest, Hungary hormone measurements in breast cancer cases. Either insulin resistance or estrogen receptor (ER) defect is the initiator of pathologic processes and both of them may lead to breast cancer development. Primary insulin resistance induces hyperandrogenism and estrogen deficiency, but during these ongoing pathologic processes, ER defect also develops. Conversely, when estrogen resistance is the onset of hormonal and metabolic disturbances, initial counteraction is For personal use only. hyperestrogenism. Compensatory mechanisms improve the damaged reactivity of ERs; however, their failure leads to secondary insulin resistance. The final stage of both pathologic pathways is the breakdown of estrogen surveillance, leading to breast cancer development. Among pre- menopausal breast cancer cases, insulin resistance is the preponderant initiator of alterations with hyperandrogenism, which is reflected by the majority of studies suggesting a causal role of hyperandrogenism in breast cancer development. In the majority of postmenopausal cases, tumor development may also be initiated by insulin resistance, while hyperandrogenism is typi- cally coupled with elevated estrogen levels within the low postmenopausal hormone range. -
Diagnostic Test: OBESITÀ GENETICHE MENDELIANE
Diagnostic test: OBESITÀ GENETICHE MENDELIANE MENDELIAN OBESITY Panel / Illumina Custom panel, Nextera Enrichment Technology / Coding exons and flanking regions of genes List of gene(s) and disease(s) tested: ALMS1, ARL6, BBIP1, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, C8orf37, CARTPT, CEP19, CEP290, DYRK1B, GNAS, HDAC8, IFT172, IFT27, INPP5E, INSR, KSR2, LEP, LEPR, LZTFL1, MC3R, MC4R, MCHR1, MEGF8, MKKS, MKS1, NR0B2, PCSK1, PHF6, POMC, PPARG, PPP1R3A, RAB23, SDCCAG8, SH2B1, SIM1, TRIM32, TTC8, UCP3, VPS13B, WDPCP ORPHA:98267 Obesità non sindromica genetica Obesità sindromica Tabella Elenco delle forme di OBESITÀ GENETICHE MENDELIANE e la loro eziologia genetica Phenotype OMIM# Gene OMIM# Phenotype Gene Alstrom syndrome 203800 ALMS1 606844 Bardet-Biedl syndrome 3 600151 ARL6 608845 Bardet-Biedl syndrome 18 615995 BBIP1 613605 Bardet-Biedl syndrome 1 209900 BBS1 209901 Bardet-Biedl syndrome 10 615987 BBS10 610148 Bardet-Biedl syndrome 12 615989 BBS12 610683 Bardet-Biedl syndrome 2 615981 BBS2 606151 Bardet-Biedl syndrome 4 615982 BBS4 600374 Bardet-Biedl syndrome 5 615983 BBS5 603650 Bardet-Biedl syndrome 7 615984 BBS7 607590 Bardet-Biedl syndrome 21 617406 C8orf37 614477 Obesity, severe HGMD CARTPT 602606 Morbid obesity and spermatogenic failure; Bardet-Biedl syndrome; Morbid obesity 615703; HGMD CEP19 615586 Bardet-Biedl syndrome 14 615991 CEP290 610142 Abdominal obesity-metabolic syndrome 3 615812 DYRK1B 604556 Pseudohypoparathyroidism Ia; Pseudohypoparathyroidism Ic 103580; 612462 GNAS 139320 Cornelia de Lange syndrome 5 300882 -
Gene Expression Profiling of Corpus Luteum Reveals the Importance Of
bioRxiv preprint doi: https://doi.org/10.1101/673558; this version posted February 27, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Gene expression profiling of corpus luteum reveals the 2 importance of immune system during early pregnancy in 3 domestic sheep. 4 Kisun Pokharel1, Jaana Peippo2 Melak Weldenegodguad1, Mervi Honkatukia2, Meng-Hua Li3*, Juha 5 Kantanen1* 6 1 Natural Resources Institute Finland (Luke), Jokioinen, Finland 7 2 Nordgen – The Nordic Genetic Resources Center, Ås, Norway 8 3 College of Animal Science and Technology, China Agriculture University, Beijing, China 9 * Correspondence: MHL, [email protected]; JK, [email protected] 10 Abstract: The majority of pregnancy loss in ruminants occurs during the preimplantation stage, which is thus 11 the most critical period determining reproductive success. While ovulation rate is the major determinant of 12 litter size in sheep, interactions among the conceptus, corpus luteum and endometrium are essential for 13 pregnancy success. Here, we performed a comparative transcriptome study by sequencing total mRNA from 14 corpus luteum (CL) collected during the preimplantation stage of pregnancy in Finnsheep, Texel and F1 15 crosses, and mapping the RNA-Seq reads to the latest Rambouillet reference genome. A total of 21,287 genes 16 were expressed in our dataset. Highly expressed autosomal genes in the CL were associated with biological 17 processes such as progesterone formation (STAR, CYP11A1, and HSD3B1) and embryo implantation (eg. -
Mouse Model of Male Germ Cell Apoptosis in Response to a Lack of Hormonal Stimulation
Indian Journal of Experimental Biology Vol. 43, November 2005, pp. 1048-1057 Mouse model of male germ cell apoptosis in response to a lack of hormonal stimulation Ami ya P Sinha Hikim*, Yanira Vera, Rashid I Elhag, Yanhe Lue, Yu-Gui Cui , Vanisha Pope, Andrew Leun g, Vince Atienza, Christina Wan g & Ron ald S Swerdloff Di vision of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center, David Geffen School of Medicine at UCLA and Los Angeles Biomedical Research Institute, Torrance. Californi a. USA Received 5 August 2005 As a prerequisite for studies using mutant mi ce, we established a mouse model for induction of male germ ce ll apoptosis after depri vation of gonadotropins and intratesti c ul ar testosterone (T). We employed a potent long acting gonadotropin-releasing hormone antagoni st (GnRH-A), acyline, al one or in combinati on with an anti and rogen, flutamide for effective inducti on of germ cell apoptosis in mice. Combined treatment with continuous release of acyline (3 mg/kg BW/day) with flutamide (in the form of sc pellets of 25 mg) resul ted in almost th e same level of suppression of spermatogenesis, as judged by testi s weight and by germ cell apoptotic index, in 2 weeks as th at re ported for rats after treatment with 1.25 mg/kg BW Nai-Giu GnRH-A for the same time peri od. Within the study paradi gm, the maximum suppression of spermatogenesis occurred after a single sc injecti on of hi gh (20 mg/kg BW) dose of acyli ne with flutamide. -
The Effect of Gonadotropin Withdrawal and Stimulation with Human Chorionic Gonadotropin on Intratesticular Androstenedione and DHEA in Normal Men
ORIGINAL ARTICLE Endocrine Research The Effect of Gonadotropin Withdrawal and Stimulation with Human Chorionic Gonadotropin on Intratesticular Androstenedione and DHEA in Normal Men M. Y. Roth, S. T. Page, K. Lin, B. D. Anawalt, A. M. Matsumoto, B. Marck, W. J. Bremner, and J. K. Amory Downloaded from https://academic.oup.com/jcem/article/96/4/1175/2720870 by guest on 02 October 2021 Departments of Internal Medicine (M.Y.R., S.T.P., B.D.A., A.M.M., W.J.B., J.K.A.) and Obstetrics and Gynecology (K.L.) and Center for Research in Reproduction and Contraception (M.Y.R., S.T.P., B.D.A., A.M.M., W.J.B., J.K.A.), University of Washington, Seattle, Washington 91895; and Geriatric Research (B.M.), Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington 98105 Introduction: Concentrations of intratesticular (IT) testosterone (T) are known to be 100–200 times those of serum T; however, the IT concentrations of T’s precursors, their testicular to serum gra- dients, gonadotropin dependence, and response to stimulation with human chorionic gonado- tropin (hCG) have not been studied in detail. We hypothesized that serum and IT androstenedione (ADD) and IT dehydroepiandrosterone (DHEA) would be significantly suppressed by the adminis- tration of a GnRH antagonist and increased when stimulated by hCG, without a similar suppression of serum DHEA. Methods: We suppressed gonadotropins in 23 normal men with the GnRH antagonist acyline and randomly assigned them to one of four doses of hCG, 0, 15, 60, or 125 IU sc every other day for 10 d. -
The Mechanism of Androgen Actions in PCOS Etiology
medical sciences Review The Mechanism of Androgen Actions in PCOS Etiology Valentina Rodriguez Paris 1 and Michael J. Bertoldo 1,2,* 1 Fertility and Research Centre, School of Women’s and Children’s Health, University of New South Wales Sydney, NSW 2052, Australia 2 School of Medical Sciences, University of New South Wales Sydney, NSW 2052, Australia * Correspondence: [email protected] Received: 15 June 2019; Accepted: 20 August 2019; Published: 28 August 2019 Abstract: Polycystic ovary syndrome (PCOS) is the most common endocrine condition in reproductive-age women. By comprising reproductive, endocrine, metabolic and psychological features—the cause of PCOS is still unknown. Consequently, there is no cure, and management is persistently suboptimal as it depends on the ad hoc management of symptoms only. Recently it has been revealed that androgens have an important role in regulating female fertility. Androgen actions are facilitated via the androgen receptor (AR) and transgenic Ar knockout mouse models have established that AR-mediated androgen actions have a part in regulating female fertility and ovarian function. Considerable evidence from human and animal studies currently reinforces the hypothesis that androgens in excess, working via the AR, play a key role in the origins of polycystic ovary syndrome (PCOS). Identifying and confirming the locations of AR-mediated actions and the molecular mechanisms involved in the development of PCOS is critical to provide the knowledge required for the future development of innovative, mechanism-based interventions for the treatment of PCOS. This review summarises fundamental scientific discoveries that have improved our knowledge of androgen actions in PCOS etiology and how this may form the future development of effective methods to reduce symptoms in patients with PCOS.