Jørn V Sagen

Jørn V Sagen
Haukeland University Hospital · Department of Medical Biochemistry and Pharmacology

M.D. Ph.D.

About

100
Publications
11,805
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2,410
Citations
Additional affiliations
April 2014 - present
Haukeland University Hospital
Position
  • Head of Department
January 2008 - December 2009
Baylor College of Medicine
Position
  • Visiting Postdoctoral Fellow
October 2005 - present
University of Bergen
Position
  • Professor (Associate)

Publications

Publications (100)
Article
Context Hormone reference intervals in pediatric endocrinology are traditionally partitioned by age and lack the framework for benchmarking individual blood test results as normalized z-scores and plotting sequential measurements onto a chart. Reference curve modeling is applicable to endocrine variables and represents a standardized method to acco...
Article
Full-text available
Context Currently there are no assays that can simultaneously quantify serum levels of the third generation aromatase inhibitors (AI); letrozole, anastrozole, and exemestane, and the ultralow levels of estrogens in postmenopausal breast cancer patients on AI treatment. Such measurements may be pivotal for the determination of optimal and individual...
Article
Full-text available
Objective Polycystic ovary syndrome (PCOS) is a common endocrine disorder, with potential effects on offspring both genetically and through altered intrauterine environment. Metformin, which ameliorate hormonal disturbances in non-pregnant women with PCOS is increasingly used in pregnancy. It passes the placenta, and the evidence on potential conse...
Article
Full-text available
Maturity‐onset diabetes of the young (MODY) is the most common type of monogenic diabetes, as it accounts for approximately 1‐2% of all cases of diabetes [1]. MODY2 is caused by mutations in the gene encoding glucokinase (GCK), whereas MODY3 is due to mutations in the hepatocyte nuclear factor 1A (HNF1A) gene. Obesity has become prevalent and the a...
Article
Full-text available
Background Diagnosing Cushing syndrome (CS) can be challenging. 24-hour urine free cortisol (UFC) measurement is considered gold standard. This is a laborious test, dependent on correct urine collection. Late-night salivary cortisol is easier, and used as a screening test for CS in adults, but has not been validated for use in children. Objective...
Article
Full-text available
Purpose The female menstrual cycle (MC) is characterized by hormonal fluctuations throughout its different phases. However, research regarding its effect on athletic performance in high level athletes is sparse. The aim of this study was to (i) investigate the female MCs effect on strength and power performance in highly trained female team athlete...
Article
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Elucidation of mechanisms that govern lipid storage, oxidative stress and insulin resistance may lead to improved therapeutic options for type 2 diabetes and other obesity-related diseases. Here, we find that adipose expression of the small neutral amino acid transporter SLC7A10, also known as alanine-serine-cysteine transporter 1 (ASC-1), shows st...
Article
Full-text available
Fibrillar collagen COL6α3 in adipose tissue has been associated with obesity, inflammation, insulin resistance and cancer. We here aimed to identify novel transcriptional regulators of COL6A3 expression. Based on a transcriptome dataset of adipose tissue, we identified strong correlations for 56 genes with COL6A3 mRNA, including targets of TGF-β/SM...
Article
Full-text available
Context: Application of ultrasound (US) to evaluate attainment and morphology of glandular tissue provides a new rationale for evaluating onset and progression of female puberty, but currently no hormone references complement this method. Further, previous studies have not explored the predictive value of endocrine profiling to determine female pu...
Article
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The World Health Organization declared COVID-19, the infectious disease caused by the coronavirus SARS-CoV-2, a pandemic on March 12, 2020. COVID-19 is causing massive health problems and economic suffering around the world. The European Association for the Study of Obesity (EASO) promptly recognised the impact that the outbreak could have on peopl...
Article
Genetic variants in HNF1B encoding the transcription factor hepatocyte nuclear factor-1 beta (HNF-1B) cause Maturity-Onset Diabetes of the Young type 5 (MODY5; HNF1B-MODY) and are the most common known monogenic cause of developmental kidney disease. The aim of this study was to assess pathogenicity of HNF1B variants identified among 312 patients s...
Article
Full-text available
Background Current analytical routine methods lack the sensitivity to monitor plasma estrogen levels in breast cancer patients treated with aromatase inhibitors. Such monitoring is warranted for premenopausal patients treated with an aromatase inhibitor and an LHRH-analogue in particular. Therefore, we aimed to develop a routine LC-MS/MS method for...
Article
Full-text available
Objective: A causal obesity risk variant in the FTO locus was recently shown to inhibit adipocyte thermogenesis via increased adipose expression of the homeobox transcription factors IRX3 and IRX5. However, causal effects of IRX5 on fat storage remain to be shown in vivo, and discovery of downstream mediators may open new therapeutic avenues. Met...
Article
Full-text available
Background: Inhibition of Irx3 and Irx5 has been shown to reduce body weight and white adipose tissue (WAT) mass through cell-autonomous and sympathetic-induced increases in adipocyte beiging and thermogenesis in mice and humans. However, the underlying mechanisms of the Irx control over beiging are still largely unknown, as illustrated by recent...
Article
Context Testicular growth represents the best clinical variable to evaluate male puberty, but current pediatric hormone references are based on chronological age and subjective assessments of discrete puberty development stages. Determination of testicular volume (TV) by ultrasound provides a novel approach to assess puberty progression and stratif...
Article
Full-text available
The objective of this study was to compare the biochemical changes related to glucose tolerance and lipid metabolism in non-diabetic patients shortly after vertical sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). Non-diabetic women and men with morbid obesity were studied the day before and six days after SG (N = 15) or RYGB (N = 16). P...
Article
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Infant and childhood growth are dynamic processes with large changes in BMI during development. By performing genome-wide association studies of BMI at 12 time points from birth to eight years (9286 children, 74,105 measurements) in the Norwegian Mother, Father, and Child Cohort Study, replicated in 5235 children, we identify a transient effect in...
Article
Full-text available
Background: Adipose tissue plays a crucial role in diet- and obesity-related insulin resistance, with implications for several metabolic diseases. Identification of novel target genes and mechanisms that regulate adipocyte function could lead to improved treatment strategies. RND3 (RhoE/Rho8), a Rho-related GTP-binding protein that inhibits Rho ki...
Article
Full-text available
Studies have implicated the extracellular matrix (ECM) of adipose tissue in insulin resistance. The proteoglycan decorin, a component of ECM, has been associated with glucose tolerance, but possible causal effects on metabolism remain to be explored. We here sought to determine metabolic consequences of loss of decorin in mice (DcnKO). DcnKO mice w...
Preprint
Full-text available
Infant and childhood growth are dynamic processes characterized by drastic changes in fat mass and body mass index (BMI) at distinct developmental stages. To elucidate how genetic variation influences these processes, we performed the first genome-wide association study (GWAS) of BMI measurements at 12 time points from birth to eight years of age (...
Poster
Full-text available
Regional, prospective and longditudinal breast cancer biobank in western Norway.
Article
Full-text available
Context Autonomous cortisol secretion (ACS) can be uni- or bilateral irrespectively of the presence of an adrenal tumor. A reliable method to discriminate between uni- and bilateral ACS is lacking. Objective Evaluate the use of adrenal venous sampling (AVS) to distinguish between uni- and bilateral ACS. Design and Methods Prospective study of AVS...
Article
Endocrine disrupting chemicals have been reported to exert effects directly on enzymes involved in steroid biosynthesis. Here, we present a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for profiling the steroid metabolome of H295R human adrenocarcinoma cells. Our method can simultaneously analyse 19 precursors, intermediates...
Article
Steroid receptor coactivator 2 (SRC-2) is a nuclear receptor coactivator, important for the regulation of estrogen receptor alpha (ERα)-mediated transcriptional activity in breast cancer cells. However, the transcriptional role of SRC-2 in breast cancer is still ambiguous. Here we aimed to unravel a more precise transcriptional role of SRC-2 and un...
Article
Adipokines secreted by fatty tissue have inflammatory properties and are suggested biomarkers of MS disease activity. To assess this, 88 MS patients were followed with nine repeated measurements of leptin and adiponectin and 12 magnetic resonance imaging (MRI) scans for two years; six months without any immunomodulatory treatment followed by 18 mon...
Article
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Background The cosyntropin test is used to diagnose adrenal insufficiency (AI) and non-classical congenital adrenal hyperplasia (NCCAH). Current cutoffs for cortisol and 17-hydroxyprogesterone (17-OHP) are derived from non-standardized immunoassays. Liquid chromatography tandem mass spectrometry (LCMSMS) offers direct measurement of steroids, promp...
Article
Primary aldosteronism (PA) is the most common cause of secondary hypertension (HT). We describe here clinical characteristics, diagnostic procedures, and long-term outcomes in a Norwegian population. All suspected PA patients investigated at a tertiary centre from 1998–2012 were retrospectively evaluated. Inclusion criteria were verified PA after c...
Article
Aims: Heterozygous mutations in hepatocyte nuclear factor-1A (HNF1A) cause maturity-onset diabetes of the young type 3 (MODY3). Our aim was to compare two families with suspected dominantly inherited diabetes and a new HNF1A variant of unknown clinical significance. Methods: The HNF1A gene was sequenced in two independently recruited families fr...
Article
Full-text available
Background: Different aspects of dietary pattern, including macronutrient and food profiles, may affect visceral fat mass and metabolic syndrome. Objective: We hypothesized that consuming energy primarily from carbohydrate or fat in diets with similar food profiles would differentially affect the ability to reverse visceral adiposity and metabol...
Article
Full-text available
The ability of the anti-diabetic drug metformin to inhibit anabolic processes including gluconeogenesis and lipogenesis is partly attributable to activation of the AMP-activated protein kinase (AMPK) pathway. The p160 steroid receptor coactivator 2 (SRC-2) is a key regulator of cellular metabolism and drives expression of the gluconeogenic enzyme g...
Article
SHORT syndrome has historically been defined by its acronym: short stature (S), hyperextensibility of joints and/or inguinal hernia (H), ocular depression (O), Rieger abnormality (R) and teething delay (T). More recently several research groups have identified PIK3R1 mutations as responsible for SHORT syndrome. Knowledge of the molecular etiology o...
Article
Full-text available
Fasting hormones activate the cAMP/PKA signaling pathway and stimulate expression of hepatic gluconeogenic enzymes including glucose-6-phosphatase (G6Pase). Previously it was shown that steroid receptor coactivator 2 (SRC-2) knock-out mice exhibit fasting hypoglycemia and that SRC-2 coactivates RAR-related orphan receptor alpha (RORα) at the proxim...
Article
Steroid Receptor Coactivator 2 (SRC-2) is a coactivator which regulates nuclear receptor activity. We previously reported that SRC-2 protein is degraded through the action of cAMP-dependent protein kinase A (PKA) and cAMP response element binding protein (CREB). In the study presented here, we aimed to identify proteins that interact with and there...
Article
ObjectiveCOL6A3 may modulate adipose tissue function in obesity and insulin resistance. A role for human adipocytes linking COL6A3 with insulin resistance warrants exploration.MethodsCOL6A3 mRNA in abdominal subcutaneous adipose samples was compared between (1) BMI-matched obese subjects resistant or sensitive to insulin (surgical whole tissue biop...
Article
Repeated attempts to lose weight by temporary dieting may result in weight cycling, eventually further gain of body fat, and possible metabolic adaptation. We tested this by a controlled experiment in C57BL/6J mice subjected to four weight cycles (WC), continuous hypercaloric feeding (HF), or low-fat feeding (LF). To search for genes involved in an...
Article
Full-text available
The p160/Steroid Receptor Coactivators SRC-1, SRC-2/GRIP1, and SRC-3/AIB1 are important regulators of Estrogen Receptor alpha (ERα) activity. However, whereas the functions of SRC-1 and SRC-3 in breast tumourigenesis have been extensively studied, little is known about the role of SRC-2. Previously, we reported that activation of the cAMP-dependent...
Data
Upregulated differentially expressed genes induced by SRC-2 shRNA. FC ≥1.5, q-value = 0. (XLSX)
Data
Primer sequences used for Q-rt-PCR. (DOC)
Data
Overlapping downregulated differentially expressed genes induced by SRC-2 shRNA and cAMP. FC ≥1.3, q-value = 0. (XLSX)
Data
Upregulated overlapping differentially expressed genes induced by SRC-2 shRNA and cAMP. FC ≥1.3, q-value = 0. (XLSX)
Data
Downregulated differentially expressed genes induced by SRC-2 shRNA. FC ≥1.5, q-value = 0. (XLSX)
Data
Downregulated differentially expressed genes induced by cAMP. FC ≥1.5, q-value = 0. (XLSX)
Data
Upregulated differentially expressed genes induced by cAMP. FC ≥1.5, q-value = 0. (XLSX)
Data
Correspondence analysis (CA) plot showing projection of microarray samples. Ctr shRNA: pink squares, SRC-2 shRNA: green diamonds, cAMP: purple circles. The first principle component is shown on the x-axis and the second principle component is displayed on the y-axis. All three groups of samples are separated along the first principle component (22....
Article
The phosphatidylinositol 3 kinase (PI3K) pathway regulates fundamental cellular processes such as metabolism, proliferation, and survival. A central component in this pathway is the p85α regulatory subunit, encoded by PIK3R1. Using whole-exome sequencing, we identified a heterozygous PIK3R1 mutation (c.1945C>T [p.Arg649Trp]) in two unrelated famili...
Article
Full-text available
Here, we review data on monogenic diabetes mellitus in Norway based on the Norwegian MODY Registry at Haukeland University Hospital, Bergen. This registry comprises established or suspected cases of maturity-onset diabetes of the young (MODY) referred to our laboratory for genetic testing. We also present data on neonatal diabetes, another group of...
Article
Full-text available
The glucocorticoid receptor interacting protein (GRIP1) belongs to the p160 steroid receptor coactivator family that plays essential roles in nuclear receptor-dependent transcriptional regulation. Previously, we reported that the cAMP-dependent protein kinase (PKA) induces ubiquitination leading to degradation of GRIP1. Here we show that the cAMP r...
Article
Full-text available
The rapidly growing family of transcriptional coregulators includes coactivators that promote transcription and corepressors that harbor the opposing function. In recent years, coregulators have emerged as important regulators of metabolic homeostasis, including the p160 steroid receptor coactivator (SRC) family. Members of the SRC family have been...
Article
Full-text available
Oxidation of lipid substrates is essential for survival in fasting and other catabolic conditions, sparing glucose for the brain and other glucose-dependent tissues. Here we show Steroid Receptor Coactivator-3 (SRC-3) plays a central role in long chain fatty acid metabolism by directly regulating carnitine/acyl-carnitine translocase (CACT) gene exp...
Article
Full-text available
Background: Adipose tissue is critical for systemic metabolic health. Identifying key factors regulating adipose tissue function is a research priority. The NR4A subfamily of nuclear receptors (NRs) (NR4A1/NUR77, NR4A2/NURR1 and NR4A3/NOR1) has emerged as important proteins in different disease states and in the regulation of metabolic tissues, pa...
Article
Breast cancer is the most frequent malignancy in women in the Western world. Hormone receptor positive breast cancers are managed with endocrine treatment in which the estrogen receptor (ER) is blocked using a selective estrogen receptor modulator (SERM) such as tamoxifen or by targeting the estrogen synthesis using aromatase inhibitors (AIs). Nucl...
Chapter
Full-text available
Breast cancer is the most frequent malignancy in women in the Western world. Hormone receptor positive breast cancers are managed with endocrine treatment in which the estrogen receptor (ER) is blocked using a selective estrogen receptor modulator (SERM) such as tamoxifen or by targeting the estrogen synthesis using aromatase inhibitors (AIs). Nucl...
Article
Gluconeogenesis makes a major contribution to hepatic glucose production, a process critical for survival in mammals. In this study, we identify the p160 family member, SRC-1, as a key coordinator of the hepatic gluconeogenic program in vivo. SRC-1-null mice displayed hypoglycemia secondary to a deficit in hepatic glucose production. Selective re-e...
Article
Hepatocyte nuclear factor-4 alpha (HNF-4alpha) is a member of the nuclear receptor superfamily with important roles in hepatic metabolism. Fasting induces the cAMP/protein kinase A (PKA)-signaling pathway. The mechanisms whereby cAMP regulates HNF-4alpha transcriptional activity are incompletely understood. We have therefore investigated the role o...