Jorma Toppari

University of Copenhagen, København, Capital Region, Denmark

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Publications (309)1187.64 Total impact

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    ABSTRACT: PCB 180 is a persistent non-dioxin-like polychlorinated biphenyl (NDL-PCB) abundantly present in food and the environment. Risk characterization of NDL-PCBs is confounded by the presence of highly potent dioxin-like impurities. We used ultrapure PCB 180 to characterize its toxicity profile in a 28-day repeat dose toxicity study in young adult rats extended to cover endocrine and behavioral effects. Using a loading dose/maintenance dose regimen, groups of 5 males and 5 females were given total doses of 0, 3, 10, 30, 100, 300, 1000 or 1700 mg PCB 180/kg body weight by gavage. Dose-responses were analyzed using benchmark dose modeling based on dose and adipose tissue PCB concentrations. Body weight gain was retarded at 1700 mg/kg during loading dosing, but recovered thereafter. The most sensitive endpoint of toxicity that was used for risk characterization was altered open field behavior in females; i.e. increased activity and distance moved in the inner zone of an open field suggesting altered emotional responses to unfamiliar environment and impaired behavioral inhibition. Other dose-dependent changes included decreased serum thyroid hormones with associated histopathological changes, altered tissue retinoid levels, decreased hematocrit and hemoglobin, decreased follicle stimulating hormone and luteinizing hormone levels in males and increased expression of DNA damage markers in liver of females. Dose-dependent hypertrophy of zona fasciculata cells was observed in adrenals suggesting activation of cortex. There were gender differences in sensitivity and toxicity profiles were partly different in males and females. PCB 180 adipose tissue concentrations were clearly above the general human population levels, but close to the levels in highly exposed populations. The results demonstrate a distinct toxicological profile of PCB 180 with lack of dioxin-like properties required for assignment of WHO toxic equivalency factor. However, PCB 180 shares several toxicological targets with dioxin-like compounds emphasizing the potential for interactions.
    PLoS ONE 08/2014; 2934495. · 3.53 Impact Factor
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    ABSTRACT: PCB 180 is a persistent non-dioxin-like polychlorinated biphenyl (NDL-PCB) abundantly present in food and the environment. Risk characterization of NDL-PCBs is confounded by the presence of highly potent dioxin-like impurities. We used ultrapure PCB 180 to characterize its toxicity profile in a 28-day repeat dose toxicity study in young adult rats extended to cover endocrine and behavioral effects. Using a loading dose/maintenance dose regimen, groups of 5 males and 5 females were given total doses of 0, 3, 10, 30, 100, 300, 1000 or 1700 mg PCB 180/kg body weight by gavage. Dose-responses were analyzed using benchmark dose modeling based on dose and adipose tissue PCB concentrations. Body weight gain was retarded at 1700 mg/kg during loading dosing, but recovered thereafter. The most sensitive endpoint of toxicity that was used for risk characterization was altered open field behavior in females; i.e. increased activity and distance moved in the inner zone of an open field suggesting altered emotional responses to unfamiliar environment and impaired behavioral inhibition. Other dose-dependent changes included decreased serum thyroid hormones with associated histopathological changes, altered tissue retinoid levels, decreased hematocrit and hemoglobin, decreased follicle stimulating hormone and luteinizing hormone levels in males and increased expression of DNA damage markers in liver of females. Dose-dependent hypertrophy of zona fasciculata cells was observed in adrenals suggesting activation of cortex. There were gender differences in sensitivity and toxicity profiles were partly different in males and females. PCB 180 adipose tissue concentrations were clearly above the general human population levels, but close to the levels in highly exposed populations. The results demonstrate a distinct toxicological profile of PCB 180 with lack of dioxin-like properties required for assignment of WHO toxic equivalency factor. However, PCB 180 shares several toxicological targets with dioxin-like compounds emphasizing the potential for interactions.
    PLoS ONE 08/2014; 9(8):e104639. · 3.53 Impact Factor
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    ABSTRACT: Although common reproductive problems, such as male infertility and testicular cancer, present in adult life, strong evidence exists that these reproductive disorders might have a fetal origin. The evidence is derived not only from large epidemiological studies that show birth-cohort effects with regard to testicular cancer, levels of testosterone and semen quality, but also from histopathological observations. Many infertile men have histological signs of testicular dysgenesis, including Sertoli-cell-only tubules, immature undifferentiated Sertoli cells, microliths and Leydig cell nodules. The most severe gonadal symptoms occur in patients with disorders of sexual development (DSDs) who have genetic mutations, in whom even sex reversal of individuals with a 46,XY DSD can occur. However, patients with severe DSDs might represent only a small proportion of DSD cases, with milder forms of testicular dysgenesis potentially induced by exposure to environmental and lifestyle factors. Interestingly, maternal smoking during pregnancy has a stronger effect on spermatogenesis than a man's own smoking. Other lifestyle factors such as alcohol consumption and obesity might also have a role. However, increasing indirect evidence exists that exposure to ubiquitous endocrine disrupting chemicals, present at measurable concentrations in individuals, might affect development of human fetal testis. If confirmed, health policies to prevent male reproductive problems should not only target adult men, but also pregnant women and their children.
    Nature Reviews Endocrinology 06/2014; · 11.03 Impact Factor
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    ABSTRACT: Background Humans are exposed to tributyltin (TBT), previously used as an antifouling paint in ships, mainly through fish consumption. As TBT is a known obesogen, we studied the association of placenta TBT and other organotin compounds (OTCs) with ponderal index (PI) and growth during the first 18 months of life in boys. Methods In a prospective Finnish study, 110 placenta samples were collected from mothers of boys born in 1997-1999 with (n = 55) and without (n = 55) cryptorchidism. To account for the original study design, linear regression, weighted for sampling fractions of boys with (121/55) and without (5677/55) cryptorchidism from the total cohort, was used to study the association between placenta OTCs and children's weight, length, growth rates and PI up to 18 months of age. Results Placenta TBT concentrations were above the limit of quantification (LOQ) in 99% of the samples. However, monobutyltin (MBT), dibutyltin (DBT) and triphenyltin (TPhT) concentrations were below LOQ in 90%, 35% and 57% of samples, respectively. Placenta TBT was positively associated (p = 0.024) with weight gain during the first three months of life, but no other significant associations were observed for weight or length gain. Also, no significant associations between placenta OTC concentrations and child length, weight or PI at any time point were found. Conclusions We observed a trend towards higher weight gain from birth to 3 months of age with increasing placenta TBT concentration. These results should be interpreted with caution because obesogenic effects in animal experiments were seen after in-utero TBT exposures to doses that were orders of magnitude higher. Also the number of study subjects included in this study was limited.
    Environmental Health 06/2014; 13(45). · 2.71 Impact Factor
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    ABSTRACT: Is there an association between alcohol intake and semen quality and serum reproductive hormones among healthy men from the USA and Europe?
    Human reproduction (Oxford, England). 06/2014;
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    ABSTRACT: Testes descend to the scrotum normally before birth. When they fail to do so, the boy is cryptorchid and has an increased risk for testicular germ cell cancer and subfertility later in life. Early correction of maldescent by orchiopexy operation improves the spermatogenetic capacity of the testis but does not return the testicular cancer risk to the control level. Testicular descent is regulated by testis-derived hormones testosterone and insulin-like peptide 3. Cryptorchidism can therefore be considered a symptom of impaired testicular function that may also be linked to other testicular diseases, such as germ cell cancer and subfertility. Early orchiopexy can alleviate the effects of cryptorchidism on spermatogenesis, but alertness for testicular cancer should be maintained. In searching the genetic and environmental reasons for these diseases, it is useful to consider their connection with each other.
    Annales d Endocrinologie 04/2014; · 1.02 Impact Factor
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    ABSTRACT: The genome of male germ cells is actively transcribed during spermatogenesis to produce phase-specific protein-coding mRNAs and a considerable amount of different noncoding RNAs. Ribonucleoprotein (RNP) granule-mediated RNA regulation provides a powerful means to secure the quality and correct expression of the requisite transcripts. Haploid spermatids are characterized by a unique, unusually large cytoplasmic granule, the chromatoid body (CB), which emerges during the switch between the meiotic and post-meiotic phases of spermatogenesis. To better understand the role of the CB in male germ cell differentiation, we isolated CBs from mouse testes and revealed its full RNA and protein composition. We showed that the CB is mainly composed of RNA-binding proteins and other proteins involved RNA regulation. The CB was loaded with RNA, including pachytene piRNAs, a diverse set of mRNAs, and a number of uncharacterized long noncoding transcripts. The CB was demonstrated to accumulate nascent RNA during all the steps of round spermatid differentiation. Our results revealed the CB as a large germ cell-specific RNP platform that is involved in the control of the highly complex transcriptome of haploid male germ cells.
    RNA 02/2014; · 5.09 Impact Factor
  • Helena E Virtanen, Jorma Toppari
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    ABSTRACT: Sexual differentiation starts with the development of bipotential gonads that further differentiate into testes or ovaries. The fetal testis secretes hormones that guide the differentiation of internal and external sex organs, whereas the fetal ovary remains rather inactive hormonally. Defects in gonadal differentiation or hormone secretion and action result in disorders of sex development (DSD). Testicular descent is a continuum that has often been described to occur in two main phases: the transabdominal phase and the inguinoscrotal phase. The first phase is according to animal studies dependent on Leydig cell-derived insulin-like peptide 3 (INSL3) that induces male-like development of the gubernaculum. This phase is rarely disrupted in man. The inguinoscrotal phase is dependent on androgens, also secreted by Leydig cells.
    Pediatric endocrinology reviews: PER 02/2014; 11 Suppl 2:206-13.
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    ABSTRACT: Research on spermatogonia is hampered by complex architecture of the seminiferous tubule, poor viability of testicular tissue ex vivo and lack of physiologically relevant long-term culture systems. Therefore there is a need for an in vitro model that would enable long term survival and propagation of spermatogonia. We aimed at the most simplified approach to enable all different cell types within the seminiferous tubules to contribute to the creation of a niche for spermatogonia. In the present study we describe the establishment of a co-culture of mouse testicular cells that is based on proliferative and migratory activity of seminiferous tubule cells and does not involve separation, purification or differential plating of individual cell populations. The co-culture is composed of the constituents of testicular stem cell niche: Sertoli cells [identified by expression of Wilm's tumour antigen 1 (WT1) and secretion of glial cell line-derived neurotrophic factor, GDNF], peritubular myoid cells (expressing alpha smooth muscle actin, αSMA) and spermatogonia [expressing MAGE-B4, PLZF (promyelocytic leukaemia zinc finger), LIN28, Gpr125 (G protein-coupled receptor 125), CD9, c-Kit and Nanog], and can be maintained for at least five weeks. GDNF was found in the medium at a sufficient concentration to support proliferating spermatogonial stem cells (SSCs) that were able to start spermatogenic differentiation after transplantation to an experimentally sterile recipient testis. Gdnf mRNA levels were elevated by follicle-stimulating hormone (FSH) which shows that the Sertoli cells in the co-culture respond to physiological stimuli. After approximately 2-4 weeks of culture a spontaneous formation of cord-like structures was monitored. These structures can be more than 10 mm in length and branch. They are formed by peritubular myoid cells, Sertoli cells, fibroblasts and spermatogonia as assessed by gene expression profiling. In conclusion, we have managed to establish in vitro conditions that allow spontaneous reconstruction of testicular cellular microenvironments.
    PLoS ONE 01/2014; 9(3):e90088. · 3.53 Impact Factor
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    ABSTRACT: Les testicules descendent normalement avant la naissance dans le scrotum. Lorsque cette migration ne s’effectue pas, le garçon est cryptorchide et présente un risque accru de cancer testiculaire et d’hypofertilité ultérieure. Une correction précoce de cette anomalie par orchidopexie améliore la spermatogenèse mais n’annule pas le risque de cancer. La migration testiculaire est régulée par les hormones testiculaires, singulièrement la testosterone et le peptide insulin-like 3. Ainsi, la cryptorchidie peut être considérée comme un symptôme de l’altération de la fonction testiculaire qui peut être également liée à d’autres maladies testiculaires comme le cancer des cellules germinales et l’hypofertilité. Une orchiopexie précoce peut corriger les effets de la cryptorchidie sur la spermatogenèse, mais le dépistage du cancer testiculaire doit être maintenu. En recherchant les causes génétiques et environnementales de ces maladies, il est utile de prendre en compte leurs interrelations.
    Annales d'Endocrinologie. 01/2014;
  • Helena Virtanen, Jorma Toppari
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    ABSTRACT: Testes descend to the scrotum normally before birth. Testis-derived testosterone and insulin-like peptide 3 (INSL3) regulate the descent. Cryptorchid testis remains too high or in an abnormal location, which prevents its normal function. The incidence of cryptorchidism varies greatly: 1 to 8% in full-term newborn boys, and 1 to 2% at three months of age. Spontaneous descent can occur during the first three months. Defective androgen action can cause cryptorchidism, but usually the etiology remains unknown. Several factors (environment, genes and lifestyle) contribute to the risk of cryptorchidism. Acquired cryptorchidism also occurs during childhood. The recommended treatment of cryptorchidism is surgical orchidopexy.
    01/2014; 130(11):1086-92.
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    ABSTRACT: The retinoblastoma protein (RB) is essential for normal cell cycle control. RB function depends, at least in part, on interactions with the E2F family of DNA-binding transcription factors (E2Fs). To study the role of RB in the adult testis, a Sertoli cell (SC)-specific Rb knockout mouse line (SC-RbKO) was generated using the Cre/loxP recombination system. SC-RbKO mice exhibited an age-dependent testicular atrophy, impaired fertility, severe SC dysfunction, and spermatogenic defects. Removal of Rb in SC induced aberrant SC cycling, dedifferentiation, and apoptosis. Here we show that E2F3 is the only E2F expressed in mouse SCs and that RB interacts with E2F3 during mouse testicular development. In the absence of RB, the other retinoblastoma family members p107 and p130 began interacting with E2F3 in the adult testes. In vivo silencing of E2F3 partially restored the SC maturation and survival as well as spermatogenesis in the SC-RbKO mice. These results point to RB as a key regulator of SC function in adult mice and that the RB/E2F3 pathway directs SC maturation, cell cycle quiescence, and RB protects SC from apoptosis.
    Cell Death & Disease 01/2014; 5:e1274. · 6.04 Impact Factor
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    ABSTRACT: Geographical differences in occurrence of diseases in male reproductive organs including malformation in reproductive tract have been reported between Denmark and Finland. The reason for these differences is unknown, but differences in exposure to chemicals with endocrine disrupting abilities have been suggested. Among these chemicals are perfluoro¬alkylated substances (PFASs) a group of water and grease repellent chemicals used in outdoor clothes, cookware, food packaging and textiles. We therefore investigated differences in PFASs exposure levels between Denmark and Finland and associated PFASs levels in cord blood with congenital cryptorchidism. Boys from a joint ongoing prospective birth cohort study were included. We analyzed PFASs levels in cord blood serum samples from 29 Danish boys with congenital cryptorchidism; 30 healthy Danish matched controls recruited from 1997-2001, 30 Finnish cases and 78 Finnish healthy matched controls recruited from 1997-1999. Additionally, 48 Finnish cases recruited from 2000-2002 were included. PFOA and PFOS were detected in all 215 Danish and Finnish cord blood samples with significantly higher levels in Danish (medians; PFOA 2.6 ng/mL, PFOS 9.1 ng/mL) compared to Finnish (medians; PFOA: 2.1 ng/mL, PFOS 5.2 ng/mL) samples. We found no associations between cord blood PFOA and PFOS levels and congenital cryptorchidism after adjustment for confounders. Our data indicate that women in Denmark and Finland are generally exposed to PFOA and PFOS but with country differences in exposure levels. We found no statistical significant association between PFOA and PFOS levels in cord blood and congenital cryptorchidism, however, our study was small and larger studies are warranted.
    Reproduction 11/2013; · 3.56 Impact Factor
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    ABSTRACT: The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU.
    Environmental Health 08/2013; 12(1):69. · 2.71 Impact Factor
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    ABSTRACT: Vitamin D is a key factor for calcium and bone homeostasis, but signalling through the vitamin D receptor (VDR) seems also to be important for testicular function. To test the functional role of vitamin D signalling we examined the male reproductive system of the Leuven Vdr-ablated (Vdr(-/-)) mice, previously established as a model for hereditary vitamin D-resistant rickets. We investigated reproductive hormones, changes in gene expression and histological phenotype of eleven Vdr(-/-), eight Vdr(+/-) and nine Vdr(+/+) mice. Testicular and epididymal histology were grossly normal in Vdr(-/-) mice. Accordingly, no differences were found in serum concentrations of testosterone, estradiol, LH, and FSH or testicular expression of Cyp19a1, Ers1, Cyp17a1, Star, Insl3, Inhbb, and Amh. However, a significantly lower ERβ expression was found in testis of Vdr(+/-) and Vdr(-/-) mice, conversely epididymal expressions of ERα and the estrogen-target gene Aqp9 were higher. In conclusion, vitamin D seems dispensable for murine spermatogenesis and sex hormone production, but aberrant estrogen-signalling may elicit some of the VDR-mediated effects on male reproduction.
    Molecular and Cellular Endocrinology 07/2013; · 4.04 Impact Factor
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    ABSTRACT: From 15-17 June 2011, a dedicated workhop was held on the subject of in vitro models for mammalian spermatogenesis and their applications in toxicological hazard and risk assessment. The workshop was sponsored by the Dutch ASAT initiative (Assuring Safety without Animal Testing), which aims at promoting innovative approaches towards toxicological hazard and risk assessment on the basis of human and in vitro data, and replacement of animal studies. Participants addressed the state of the art regarding human and animal evidence for compound mediated testicular toxicity, reviewed existing alternative assay models, and brainstormed about future approaches, specifically considering tissue engineering. The workshop recognized the specific complexity of testicular function exemplified by dedicated cell types with distinct functionalities, as well as different cell compartments in terms of microenvironment and extracellular matrix components. This complexity hampers quick results in the realm of alternative models. Nevertheless, progress has been achieved in recent years, and innovative approaches in tissue engineering may open new avenues for mimicking testicular function in vitro. Although feasible, significant investment is deemed essential to be able to bring new ideas into practice in the laboratory. For the advancement of in vitro testicular toxicity testing, one of the most sensitive end points in regulatory reproductive toxicity testing, such an investment is highly desirable.
    Reproductive Toxicology 04/2013; · 3.14 Impact Factor
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    Environmental Health Perspectives 04/2013; 121(4):a104-6. · 7.26 Impact Factor
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    ABSTRACT: STUDY QUESTION: Is the placental burden of organotin compounds (OTCs) associated with congenital cryptorchidism in infant offspring from Finland and Denmark? SUMMARY ANSWER: Increasing concentrations of OTCs had a negative association with cryptorchidism in Finland, whereas a positive association was found in Denmark. WHAT IS KNOWN ALREADY: The rapid increase in the prevalence of cryptorchidism suggests that environmental factors, such as endocrine disruptors, may be involved. OTCs are endocrine disruptors at very low concentrations due to activation of the retinoid X receptor (RXR). STUDY DESIGN, SIZE, DURATION: Between the years 1997 and 2001, placentas from mothers of cryptorchid boys and from healthy controls were collected from Denmark (39 cases, 129 controls) and Finland (56 cases, 56 controls). In Denmark 33 and 6 boys, and in Finland 22 and 34 boys had mild or severe cryptorchidism, respectively. The association between concentrations of four OTCs [monobutyltin (MBT), dibutyltin (DBT), tributyltin (TBT) and triphenyltin (TPhT)] and case-control status was estimated. PARTICIPANTS/MATERIALS, SETTING, METHODS: In both countries, placenta samples were selected from larger cohorts. In Finland placenta samples were collected from boys with cryptorchidism at birth and matched controls (nested case-control design). Matching criteria were parity, maternal smoking (yes/no), diabetes (yes/no), gestational age (±7 days) and date of birth (±14 days). Numbers of controls per case was 1. In Denmark, all available placentas from cryptorchid boys were chosen and control placentas were selected randomly from the total Danish cohort (case-cohort design). The average number of controls per case was 3.3. OTCs in placenta samples were analysed with liquid extraction, ethylation and gas chromatography-mass spectrometry determination and coded by country-specific tertiles. MAIN RESULTS AND THE ROLE OF CHANCE: Generally, the concentrations of OTCs were very low. For most analytes, a large proportion of samples (29-96% depending on the country and case-control status) had OTC concentrations below the limit of quantification (LOQ). As an exception, the concentration of TBT was >LOQ in 99% of Finnish placentas. The mean concentrations of DBT and TBT were 1.5 and 7 times higher in Finland than in Denmark, respectively. For DBT in Danish placentas, the odds ratio (OR) for cryptorchidism in the second tertile (0.10-0.14 ng/g) when compared with the first tertile (<0.10 ng/g, <LOQ) was 3.13 (95% CI 1.19-8.26) and the OR for the third tertile (≥0.15 ng/g) when compared with the first tertile was 4.01 (95% CI 1.42-11.33). For TBT in Finnish placentas, the OR for cryptorchidism in the second tertile (0.10-0.39 ng/g) when compared with the first tertile (<0.1 ng/g) was 0.61 (95% CI 0.18-2.01) and the OR for the third tertile (≥0.40 ng/g) when compared with the first tertile was 0.13 (95% CI 0.03-0.54). LIMITATIONS, REASONS FOR CAUTION: The main limitation of the study was the relatively small number of mother-boy pairs that limits the extrapolation of the study results to the general population. Also misclassification of exposure is a reason for caution for two reasons: because the concentrations of most OTCs were below or only barely above the LOQ in a large proportion of samples and because it is not known how well OTCs measured from placenta represent exposure at the time window that is relevant for cryptorchidism occurrence. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to measure the concentrations of OTCs from human placenta samples, and to associate these concentrations to cryptorchidism. As opposite results were obtained with regard to OTC concentration in placenta and cryptorchidism status in Finland and Denmark, and no mechanism is known at the moment by which OTCs could affect testicular descent, these results cannot be generalized to other populations. However, some animal tests described in the literature show opposite effects of OTCs on fat deposition at different ranges of exposure. It is also clearly shown in the literature that TBT has an impact on sexual development of gastropods through RXR. As TBT is known to activate human RXR, further laboratory studies should be designed to explore the potential impact of TBT on male sexual development. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the European Commission (QLK4-CT-1999-01422, QLK4-CT-2001-00269, QLK4-2002-0063, FP7/2008-2012: DEER 212844), The Danish Medical Research Council (9700833, 9700909), Danish Agency for Science (Technology and Innovation 09-067180), the Svend Andersen's Foundation, Velux Foundation and Novo Nordisk Foundation, the Turku University Central Hospital, Sigrid Jusélius Foundation and the Academy of Finland.There are no competing financial, personal or professional interests.
    Human Reproduction 03/2013; · 4.67 Impact Factor
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    ABSTRACT: A link between elevated LH levels, GATA-4 and luteinizing hormone receptor (LHCGR) expression and gonadotropin-dependent adrenocortical tumorigenesis in humans and mice has been shown. To assess the mechanistic tumorigenic interrelationships between these factors, we transgenically expressed Gata4 under the 21-hydroxylase promoter (Cyp21a1, 21-OH) in C57Bl/6N mice. There was a gradual age-dependent increase of GATA-4 expression only in 21-OH-GATA-4 (TG) female adrenals, in association with slowly progressing neoplasia of non-steroidogenic spindle-shaped A cells in the subcapsular cortex. Gonadectomy (GDX), apparently through direct action of elevated serum LH, markedly enhanced the adrenocortical neoplasia, which now also appeared in GDX TG males. The neoplastic areas of the post-GDX TG adrenals contained, besides A cells, larger lipid-laden, steroidogenically active and LHCGR positive B cells. Prolonged (>10 months, mo) exposure to elevated post-GDX LH levels resulted in formation of adrenocortical adenomas in the TG mice. Intact and GDX TG mouse adrenals displayed elevated FOG-2 and decreased GATA-6 expression. Additionally, increased expression/activation of components of the Inhbb-Acvr2a-Acvr1c-Smad2/3 signaling system was observed in 12-mo-old GDX TG adrenals. Our findings showed the formation of two distinct GATA-4-dependent populations of neoplastic adrenocortical cells: non-steroidogenic, LH-independent A cells and steroidogenic, LH-dependent B cells.
    Journal of Cell Science 02/2013; · 5.88 Impact Factor

Publication Stats

9k Citations
1,187.64 Total Impact Points

Institutions

  • 2006–2014
    • University of Copenhagen
      • • Faculty of Health and Medical Sciences
      • • Section of Biostatistics
      København, Capital Region, Denmark
  • 1970–2014
    • University of Turku
      • • Department of Physiology
      • • Department of Paediatrics
      • • Institute of Biomedicine
      • • Department of Medical Biochemistry and Genetics
      Turku, Province of Western Finland, Finland
  • 2013
    • National Institute for Health and Welfare, Finland
      • Department of Environmental Health
      Helsinki, Province of Southern Finland, Finland
    • St. Marianna University School of Medicine
      • Department of Urology
      Kawasaki, Kanagawa-ken, Japan
  • 2012
    • The University of Edinburgh
      • MRC Centre for Reproductive Health
      Edinburgh, Scotland, United Kingdom
  • 2009–2012
    • Technical University of Denmark
      • Center for Biological Sequence Analysis
      Copenhagen, Capital Region, Denmark
    • MTT Agrifood Research
      • Biotechnology and Food Research Unit
      Jokioinen, Province of Southern Finland, Finland
  • 2007–2012
    • University of Helsinki
      • Institute of Biomedicine
      Helsinki, Province of Southern Finland, Finland
    • University of Washington Seattle
      • Department of Pediatrics
      Seattle, WA, United States
  • 2011
    • Imperial College London
      • Department of Surgery and Cancer
      London, ENG, United Kingdom
    • Washington University in St. Louis
      • Department of Pediatrics
      Saint Louis, MO, United States
    • Helsinki University Central Hospital
      • Children's Hospital
      Helsinki, Province of Southern Finland, Finland
  • 2007–2011
    • Region Hovedstaden
      Hillerød, Capital Region, Denmark
  • 2008
    • University of Santiago de Compostela
      • Departamento de Fisiología
      Santiago de Compostela, Galicia, Spain
    • University of Tampere
      • Medical School
      Tampere, Western Finland, Finland
    • University of Kuopio
      Kuopio, Eastern Finland Province, Finland
    • University of California, Davis
      • Department of Environmental Toxicology
      Davis, CA, United States
    • Turku University Hospital
      • Department of Pediatrics
      Turku, Western Finland, Finland
  • 2003–2006
    • University of Cordoba (Spain)
      • • Departamento de Biología Celular, Fisiología e Inmunología
      • • Facultad de Medicina
      Córdoba, Andalusia, Spain
  • 2005
    • Kaunas University of Technology
      Caunas, Kauno Apskritis, Lithuania
  • 2004
    • University of Southern Denmark
      Odense, South Denmark, Denmark
  • 2002–2004
    • Rigshospitalet
      • Department of Growth and Reproduction
      København, Capital Region, Denmark
  • 1989–2003
    • Harbor-UCLA Medical Center
      • Department of Pediatrics
      Torrance, California, United States
  • 2000
    • Odense University Hospital
      Odense, South Denmark, Denmark
  • 1991
    • Karolinska University Hospital
      • Endocrinology Unit
      Stockholm, Stockholm, Sweden
  • 1990–1991
    • University of Southern California
      • • Department of Medicine
      • • Department of Obstetrics and Gynecology
      Los Angeles, CA, United States
    • Stockholm University
      • Department of Biochemistry and Biophysics
      Stockholm, Stockholm, Sweden
  • 1988
    • Keck School of Medicine USC
      Los Angeles, California, United States