Publications
932 results found
Oksala R, Moilanen A, Riikonen R, et al., 2015, ODM-204: A novel dual inhibitor of CYP17A1 and androgen receptor for the treatment of castration-resistant prostate cancer-Preclinical data., Genitourinary Cancers Symposium, Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
Teerds KJ, Huhtaniemi IT, 2015, Morphological and functional maturation of Leydig cells: from rodent models to primates, HUMAN REPRODUCTION UPDATE, Vol: 21, Pages: 310-328, ISSN: 1355-4786
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- Citations: 102
Jonas KC, Fanelli F, Huhtaniemi IT, et al., 2015, Single molecule analysis of functionally asymmetric G protein-coupled receptor (GPCR) oligomers reveals diverse spatial and structural assemblies, Journal of Biological Chemistry, Vol: 290, Pages: 3875-3892, ISSN: 1083-351X
Background: GPCRs form complex oligomers whose role in signaling is poorly understood.Results: Super-resolution imaging of functionally asymmetric oligomers reveals diverse functional and structural organizationsand the ability to alter signal responses.Conclusion: GPCR oligomers may fine-tune receptor signaling by altering the functional role of individual protomers.Significance: Distinct oligomers could be exploited pharmacologically to improve efficacy, selectivity, and/or specificity.
Bjorkgren I, Gylling H, Turunen H, et al., 2015, Imbalanced lipid homeostasis in the conditional Dicer1 knockout mouse epididymis causes instability of the sperm membrane, FASEB JOURNAL, Vol: 29, Pages: 433-442, ISSN: 0892-6638
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- Citations: 41
Han TS, Lee DM, Lean MEJ, et al., 2015, Associations of obesity with socioeconomic and lifestyle factors in middle-aged and elderly men: European Male Aging Study (EMAS), EUROPEAN JOURNAL OF ENDOCRINOLOGY, Vol: 172, ISSN: 0804-4643
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- Citations: 16
Trehan A, Rotgers E, Coffey ET, et al., 2014, CANDLES, an assay for monitoring GPCR induced cAMP generation in cell cultures, Cell Communication and Signaling, Vol: 12
Trehan A, Rotgers E, Coffey ET, et al., 2014, CANDLES, an assay for monitoring GPCR induced cAMP generation in cell cultures, Cell Communication and Signaling, Vol: 12, ISSN: 1478-811X
Background: G protein-coupled receptors (GPCRs) represent a physiologically and pharmacologically importantfamily of receptors that upon coupling to GαS stimulate cAMP production catalyzed by adenylyl cyclase. Thus,developing assays to monitor cAMP production is crucial to screen for ligands in studies of GPCR signaling. Primarycell cultures represent a more robust model than cell lines to study GPCR signaling since they physiologicallyresemble the parent tissue. Current cAMP assays have two fundamental limitations: 1) absence of cAMP kinetics ascompetition-based assays require cell lysis and measure only a single time-point, and 2) high variation with separatesamples needed to measure consecutive time points. The utility of real-time cAMP biosensors is also limited inprimary cell cultures due to their poor transfection efficiency, variable expression levels and inability to select stableclones. We therefore, decided to develop an assay that can measure cAMP not only at a single time-point but theentire cAMP kinetics after GPCR activation in untransfected primary cells.Results: CANDLES (Cyclic AMP iNdirect Detection by Light Emission from Sensor cells) assay for monitoring cAMPkinetics in cell cultures, particularly in primary cultures was developed. The assay requires co-culturing of primarycells with sensor cells that stably express a luminescent cAMP sensor. Upon GPCR activation in primary cells, cAMPis transferred to sensor cells via gap junction channels, thereby evoking a luminescent read-out. GPCR activationusing primary cultures of rat cortical neurons and mouse granulosa cells was measured. Kinetic responses of differentagonists to adrenergic receptors were also compared using rat cortical neurons. The assay optimization was done byvarying sensor-test cell ratio, using phosphodiesterase inhibitors and testing cell-cell contact requirement.Conclusions: Here we present CANDLES assay based on co-culturing test cells with cAMP-detecting sensor cells.This
Abel MH, Widen A, Wang X, et al., 2014, Pituitary Gonadotrophic Hormone Synthesis, Secretion, Subunit Gene Expression and Cell Structure in Normal and Follicle-Stimulating Hormone β Knockout, Follicle-Stimulating Hormone Receptor Knockout, Luteinising Hormone Receptor Knockout, Hypogonadal and Ovariectomised Female Mice, JOURNAL OF NEUROENDOCRINOLOGY, Vol: 26, Pages: 785-795, ISSN: 0953-8194
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- Citations: 8
Holgersson MB, Giwercman A, Bjartell A, et al., 2014, Androgen Receptor Polymorphism-Dependent Variation in Prostate-Specific Antigen Concentrations of European Men, CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, Vol: 23, Pages: 2048-2056, ISSN: 1055-9965
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- Citations: 7
Jonas KC, Oduwole OO, Peltoketo H, et al., 2014, Mouse models of altered gonadotrophin action: insight into male reproductive disorders, REPRODUCTION, Vol: 148, Pages: R63-R70, ISSN: 1470-1626
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- Citations: 19
Lee DM, Vanderschueren D, Boonen S, et al., 2014, Association of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone with mortality among middle-aged and older European men, AGE AND AGEING, Vol: 43, Pages: 528-535, ISSN: 0002-0729
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- Citations: 20
Ulloa-Aguirre A, Reiter E, Bousfield G, et al., 2014, Constitutive activity in gonadotropin receptors., Adv Pharmacol, Vol: 70, Pages: 37-80
Constitutively active mutants (CAMs) of gonadotropin receptors are, in general, rare conditions. Luteinizing hormone-choriogonadotropin receptor (LHCGR) CAMs provoke the dramatic phenotype of familial gonadotropin-independent isosexual male-limited precocious puberty, whereas in females, there is not yet any identified phenotype. Only one isolated follicle-stimulating hormone receptor (FSHR) CAM (Asp567Gly) has so far been detected in a single male patient, besides other FSHR weak CAMs linked to pregnancy-associated ovarian hyperstimulation syndrome or to impaired desensitization and internalization. Several animal models have been developed for studying enhanced gonadotropin action; in addition to unraveling valuable new information about the possible phenotypes of isolated FSHR and LHCGR CAMs in women, the information obtained from these mouse models has served multiple translational goals, including the development of new diagnostic and therapeutic targets as well as the prediction of phenotypes for mutations not yet identified in humans. Mutagenesis and computational studies have shed important information on the physiopathogenic mechanisms leading to constitutive activity of gonadotropin receptors; a common feature in these receptor CAMs is the release of stabilizing interhelical interactions between transmembrane domains (TMDs) 3 and 6 leading to an increase, with respect to the wild-type receptor, in the solvent accessibility at the cytosolic extension of TMDs 3, 5, and 6, which involves the highly conserved Glu/Asp-Arg-Tyr/Trp sequence. In this chapter, we summarize the structural features, functional consequences, and mechanisms that lead to constitutive activation of gonadotropin receptor CAMs and provide information on pharmacological approaches that might potentially modulate gonadotropin receptor CAM function.
Gonzalez B, Ratner LD, Scerbo MJ, et al., 2014, Elevated hypothalamic aromatization at the onset of precocious puberty in transgenic female mice hypersecreting human chorionic gonadotropin: Effect of androgens, MOLECULAR AND CELLULAR ENDOCRINOLOGY, Vol: 390, Pages: 102-111, ISSN: 0303-7207
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- Citations: 6
Canoy D, Barber TM, Pouta A, et al., 2014, Serum sex hormone-binding globulin and testosterone in relation to cardiovascular disease risk factors in young men: a population-based study, EUROPEAN JOURNAL OF ENDOCRINOLOGY, Vol: 170, Pages: 863-872, ISSN: 0804-4643
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- Citations: 30
Trehan A, Rotgers E, Coffey E, et al., 2014, Bioassay to Monitor cAMP Production in Primary Cell Cultures, ENDOCRINE REVIEWS, Vol: 35, ISSN: 0163-769X
Jonas KC, Fanelli F, Huhtaniemi IT, et al., 2014, Single Molecule Analysis of GPCR Transactivation Via PD-PALM Reveals Oligomeric Complexes That Regulate Signal Sensitivity, ENDOCRINE REVIEWS, Vol: 35, ISSN: 0163-769X
Antonio L, Wu FC, O'Neill TN, et al., 2014, Low Serum Testosterone and Its Aromatisation into Estradiol Increases Risk for Metabolic Syndrome in Men Independent of SHBG, ENDOCRINE REVIEWS, Vol: 35, ISSN: 0163-769X
Carter EL, Finn JD, Pye SR, et al., 2014, Natural History of the Development Compensated Hypogonadism in Eugonadal Ageing Men: Predisposing Factors, and Potential Clinical Significance - Longitudinal Data from the European Male Ageing Study (EMAS), ENDOCRINE REVIEWS, Vol: 35, ISSN: 0163-769X
Huhtaniemi IT, Carter EL, Finn JD, et al., 2014, Natural History of the Progression of Compensated Hypogonadism to Primary Hypogonadism in Ageing Men: Hormonal and Phenotypic Characteristics Longitudinal Data from the European Male Ageing Study (EMAS), ENDOCRINE REVIEWS, Vol: 35, ISSN: 0163-769X
Oduwole OO, Vydra N, Wood NEM, et al., 2014, Overlapping dose responses of spermatogenic and extragonadal testosterone actions jeopardize the principle of hormonal male contraception, FASEB JOURNAL, Vol: 28, Pages: 2566-2576, ISSN: 0892-6638
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- Citations: 17
Rotgers E, Rivero-Muller A, Nurmio M, et al., 2014, Retinoblastoma protein (RB) interacts with E2F3 to control terminal differentiation of Sertoli cells, CELL DEATH & DISEASE, Vol: 5, ISSN: 2041-4889
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- Citations: 18
Huhtaniemi IT, 2014, Andropause - lessons from the European Male Ageing Study, ANNALES D ENDOCRINOLOGIE, Vol: 75, Pages: 128-131, ISSN: 0003-4266
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- Citations: 17
Pye SR, Huhtaniemi IT, Finn JD, et al., 2014, Late-Onset Hypogonadism and Mortality in Aging Men, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 99, Pages: 1357-1366, ISSN: 0021-972X
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- Citations: 133
Ploeckinger U, Tiling N, Blankenstein O, et al., 2014, Transient pregnancy-induced Cushing's Syndrome with Aberrant Adrenal hCG receptor, EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES, Vol: 122, ISSN: 0947-7349
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- Citations: 1
Huhtaniemi I, 2014, Late-onset hypogonadism: current concepts and controversies of pathogenesis, diagnosis and treatment, ASIAN JOURNAL OF ANDROLOGY, Vol: 16, Pages: 192-202, ISSN: 1008-682X
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- Citations: 131
Ratner LD, Rulli SB, Huhtaniemi IT, 2014, Genetically modified mouse models addressing gonadotropin function, REPRODUCTIVE BIOLOGY, Vol: 14, Pages: 9-15, ISSN: 1642-431X
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- Citations: 5
Chrusciel M, Doroszko M, Stelmaszewska J, et al., 2014, Transgenic mice expressing inhibin α-subunit promoter (inhα)/Simian Virus 40 T-antigen (Tag) transgene as a model for the therapy of granulosa cell-derived ovarian cancer, REPRODUCTIVE BIOLOGY, Vol: 14, Pages: 25-31, ISSN: 1642-431X
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- Citations: 5
Corona G, Wu FC, Rastrelli G, et al., 2014, Low Prolactin Is Associated with Sexual Dysfunction and Psychological or Metabolic Disturbances in Middle-Aged and Elderly Men: The European Male Aging Study (EMAS), JOURNAL OF SEXUAL MEDICINE, Vol: 11, Pages: 240-253, ISSN: 1743-6095
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- Citations: 58
Corona G, Wu F, Rastrelli G, et al., 2014, LOW PROLACTIN IS ASSOCIATED WITH SEXUAL DYSFUNCTION AND PSYCHOLOGICAL OR METABOLIC DISTURBANCES IN MIDDLE AGED AND ELDERLY MEN: THE EUROPEAN MALE AGING STUDY (EMAS), Publisher: WILEY-BLACKWELL, Pages: 8-8, ISSN: 1743-6095
Corona G, Wu FC, Rastrelli G, et al., 2014, Low prolactin is associated with sexual dysfunction and psychological or metabolic disturbances in middle-aged and elderly men: the European Male Aging Study (EMAS)., J Sex Med, Vol: 11, Pages: 240-253
INTRODUCTION: We previously reported that in male patients consulting for sexual dysfunction, low prolactin (PRL) levels were associated with metabolic syndrome (MetS), arteriogenic erectile dysfunction, and incident major cardiovascular events. AIM: The aim of this study is to assess the clinical associations of PRL levels in the European Male Ageing Study (EMAS). METHODS: EMAS is a prospective, observational cohort of community-dwelling men aged 40-79 years old (mean age 60 ± 11 years old). PRL was available for 2,948 men. MAIN OUTCOME MEASURES: Different parameters were evaluated including the Short Form-36 questionnaire, Becks Depression Inventory, the Adverse Life Events Scale, the Physical Activity Scale for the Elderly, and the EMAS sexual function questionnaire (EMAS-SFQ). RESULTS: After the adjustment for confounders, PRL levels were inversely related with worsening of sexual function as compared with the previous year, as derived from change in sexual functioning domain of the EMAS-SFQ (adj. r = -0.043; P = 0.029). The strongest correlation (Wald = 6.840; P = 0.009) was observed between lower PRL levels and reduced enjoyment of orgasmic experiences. Furthermore, an inverse relationship between PRL levels and stressful life events or depressive symptoms was observed. Low PRL was also negatively associated with an unhealthy metabolic phenotype as well as with the MetS (Wald = 5.229; P = 0.022). In line with these data, low PRL was associated with a lower level of physical activity and feeling unhealthier. CONCLUSIONS: Low PRL is related to several metabolic, psychological, and sexual unhealthy characteristics in European men. Checking PRL might be useful to stratify men for cardiovascular risk and to encourage appropriate lifestyle changes.
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