A5013160218- Hypothalamic control of reproductive hormones
- Sexual Differentiation and Disorders
- Ovarian function and disorders
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Fibroblast Growth Factor Research
- Hormonal and reproductive studies
- Growth Hormone and Insulin-like Growth Factors
- Plant Reproductive Biology
- Sperm and Testicular Function
- Genetic Syndromes and Imprinting
- Pituitary Gland Disorders and Treatments
- Regulation of Appetite and Obesity
- Stress Responses and Cortisol
- Birth, Development, and Health
- Congenital Ear and Nasal Anomalies
- Genomics and Chromatin Dynamics
- Thyroid Disorders and Treatments
- Diet and metabolism studies
- Adipose Tissue and Metabolism
- Epigenetics and DNA Methylation
- Adolescent and Pediatric Healthcare
- Animal Nutrition and Physiology
- Kruppel-like factors research
- Diabetes and associated disorders
- Diabetes Management and Research
University Hospital of Lausanne
2016-2025
University of Lausanne
2016-2025
Copenhagen University Hospital
2023
Praevium Research (United States)
2023
Children's Hospital of Philadelphia
2023
Rigshospitalet
2023
Endocrinology Research Center
2018
Hôpital Orthopédique de la Suisse Romande
2016
Diabetes Australia
2015
Brigham and Women's Hospital
2010-2015
Insulin resistance is associated with low testosterone (T) levels in men, the mechanism of which unclear. Thus, aim this study was to evaluate hypothalamic-pituitary-gonadal axis men a spectrum insulin sensitivity. Twenty-one (aged 25–65 yr) had glucose tolerance test and assessment sensitivity using hyperinsulinemic-euglycemic clamp. sensitivity, expressed as M value (milligrams per kilograms−1 minute−1), calculated from disposal rate during final 30 min Eighteen subjects blood sampling...
OBJECTIVE— The goal of this study was to examine the relationship between serum testosterone levels and insulin sensitivity mitochondrial function in men. RESEARCH DESIGN AND METHODS—A total 60 men (mean age 60.5 ± 1.2 years) had a detailed hormonal metabolic evaluation. Insulin measured using hyperinsulinemic-euglycemic clamp. Mitochondrial assessed by measuring maximal aerobic capacity (Vo2max) expression oxidative phosphorylation genes skeletal muscle. RESULTS—A 45% subjects normal...
Idiopathic hypogonadotropic hypogonadism, which may be associated with anosmia (the Kallmann syndrome) or a normal sense of smell, is treatable form male infertility caused by congenital defect in the secretion action gonadotropin-releasing hormone (GnRH). Patients have absent incomplete sexual maturation age 18. hypogonadism was previously thought to require lifelong therapy. We describe 15 men whom reversal idiopathic sustained after discontinuation hormonal therapy.We defined as presence...
Idiopathic hypogonadotropic hypogonadism (IHH) with anosmia (Kallmann syndrome; KS) or a normal sense of smell (normosmic IHH; nIHH) are heterogeneous genetic disorders associated deficiency gonadotropin-releasing hormone (GnRH). While loss-of-function mutations in FGF receptor 1 (FGFR1) cause human GnRH deficiency, to date no specific ligand for FGFR1 has been identified neuron ontogeny. Using candidate gene approach, we 6 missense FGF8 IHH probands variable olfactory phenotypes. These...
Idiopathic hypogonadotropic hypogonadism (IHH) due to defects of gonadotropin-releasing hormone (GnRH) secretion and/or action is a developmental disorder sexual maturation. To date, several single-gene have been implicated in the pathogenesis IHH. However, significant inter- and intrafamilial variability apparent incomplete penetrance familial cases IHH are difficult reconcile with model defect. We therefore hypothesized that mutations at different loci interact some families modify their...
Between the genetic extremes of rare monogenic and common polygenic diseases lie diverse oligogenic disorders involving mutations in more than one locus each affected individual. Elucidating principles inheritance mechanisms interactions could help unravel newly appreciated role sequence variants disorders. With few exceptions, however, precise architecture remains unknown. Isolated gonadotropin-releasing hormone (GnRH) deficiency caused by defective secretion or action hypothalamic GnRH is...
Functional hypothalamic amenorrhea is a reversible form of gonadotropin-releasing hormone (GnRH) deficiency commonly triggered by stressors such as excessive exercise, nutritional deficits, or psychological distress. Women vary in their susceptibility to inhibition the reproductive axis stressors, but it unknown whether this variability reflects genetic predisposition amenorrhea. We hypothesized that mutations genes involved idiopathic hypogonadotropic hypogonadism, congenital GnRH...
Gonadotropin-releasing hormone (GnRH) deficiency in the human presents either as normosmic idiopathic hypogonadotropic hypogonadism (nIHH) or with anosmia [Kallmann syndrome (KS)]. To date, several loci have been identified to cause these disorders, but only 30% of cases exhibit mutations known genes. Recently, murine studies demonstrated a critical role prokineticin pathway olfactory bulb morphogenesis and GnRH secretion. Therefore, we hypothesize that 2 ( PROK2 ) underlie some KS humans...
Mutations in KAL1 and FGFR1 cause Kallmann syndrome (KS), whereas mutations the GNRHR GPR54 genes idiopathic hypogonadotropic hypogonadism with normal olfaction (nIHH). Mixed pedigrees containing both KS nIHH have also been described; however, genetic of these rare cases is unknown. We examined gene seven subjects who either belonged to a mixed pedigree (n = 5) or had associated midline defects 2). Heterozygous were found three unrelated probands MRI olfactory system: (i) G237S an female...
GnRH treatment is successful in inducing virilization and spermatogenesis men with idiopathic hypogonadotropic hypogonadism (IHH). However, a small subset of IHH men, poorly characterized to date, fail reach normal testicular volume (TV) produce sperm on this therapy. To determine predictors outcome terms TV count, we studied 76 (38% anosmia) undergoing therapy for 12–24 months. The population was stratified according the baseline degree prior pubertal development: absent (group 1, n = 52),...
Evidence suggests that testosterone (T) influences insulin sensitivity in men. The mechanism of this effect is unclear but thought to involve changes body composition.The aim study was determine whether acute sex steroid withdrawal decreases young, healthy men with idiopathic hypogonadotropic hypogonadism (IHH).This a 2-wk prospective study.The conducted at General Clinical Research Center.Twelve IHH (age 40.8 +/- 2.8 yr) were studied: 1) on hormone replacement normal T levels and 2) 2 wk...
Mutations in the GnRH receptor (GNRHR) have been described as a cause of reproductive failure subset patients with idiopathic hypogonadotropic hypogonadism (IHH). Given apparent rarity these mutations, we set out to determine frequency and distribution GNRHR mutations heterogeneous population IHH who were well characterized respect diagnosis, phenotype, mode inheritance define their within protein. One hundred eight probands screened for coding sequence GNRHR. Forty-eight 108 had normal...
Kallmann syndrome (KS) is the combination of hypogonadotropic hypogonadism and anosmia or hyposmia, two features that are also frequently present in CHARGE syndrome. caused by mutations CHD7 gene. We performed analysis 36 patients with KS 20 normosmic idiopathic (nIHH) whom KAL1 , FGFR1 PROK2 PROKR2 genes were excluded. Three 56 KS/nIHH had de novo . In retrospect, these three ‐positive showed additional seen can be who have part phenotype. did not find isolated KS. These findings imply...
Mice deficient in prokineticin 2(PROK2) and receptor2 (PROKR2) exhibit variable olfactory bulb dysgenesis GnRH neuronal migration defects reminiscent of human deficiency.We aimed to screen a large cohort patients with Kallmann syndrome (KS) normosmic idiopathic hypogonadotropic hypogonadism (IHH) for mutations PROK2/PROKR2, evaluate their prevalence, define the genotype/phenotype relationship, assess functionality these mutant alleles vitro.Sequencing PROK2 PROKR2 genes was performed 170 KS...
As our knowledge of the molecular mechanisms underlying idiopathic hypogonadotropic hypogonadism (IHH) expands, it becomes increasingly important to define phenotypic spectrum IHH. In this study we examined historical, clinical, biochemical, histological, and genetic features in 78 men with IHH gain further insight into heterogeneity syndrome. We hypothesized that at least some phenotypes could be explained by placing disorder a developmental context. Thirty-eight percent population had...
Idiopathic hypogonadotropic hypogonadism (IHH) is a condition characterized by failure to undergo puberty in the setting of low sex steroids and gonadotropins. IHH due abnormal secretion or action master reproductive hormone gonadotropin-releasing (GnRH). Several genes have been found be mutated patients with IHH, yet date no mutations identified most obvious candidate gene, GNRH1 itself, which encodes preprohormone that ultimately processed produce GnRH. We screened DNA from 310 normosmic...
The complexity of genetic testing in Kallmann syndrome (KS) is growing and costly. Thus, it important to leverage the clinical evaluations KS patients prioritize screening.The objective study was determine which reproductive nonreproductive phenotypes subjects have implications for specific gene mutations.Two hundred nineteen were studied: 151 with identified rare sequence variants (RSVs) 8 genes known cause (KAL1, NELF, CHD7, HS6ST1, FGF8/FGFR1, or PROK2/PROKR2) 68 who remain RSV negative...
Neuronal development is the result of a multitude neural migrations, which require extensive cell-cell communication. These processes are modulated by extracellular matrix components, such as heparan sulfate (HS) polysaccharides. HS molecularly complex nonrandom modifications sugar moieties, including sulfations in specific positions. We report here mutations 6-O-sulfotransferase 1 ( HS6ST1 ) families with idiopathic hypogonadotropic hypogonadism (IHH). IHH manifests incomplete or absent...
A subset of patients diagnosed with idiopathic hypogonadotropic hypogonadism (IHH) later achieves activation their hypothalamic-pituitary-gonadal axis normalization steroidogenesis and/or gametogenesis, a phenomenon termed reversal.The objective this study was to determine the natural history reversal and identify associated phenotypes genotypes.This retrospective review clinical, biochemical, genetic features IHH evaluated at an academic medical center.History spontaneous fertility, regular...
Kallmann syndrome (KS), combined pituitary hormone deficiency (CPHD), and septo-optic dysplasia (SOD) all result from development defects of the anterior midline in human forebrain.The objective study was to investigate whether KS, CPHD, SOD have shared genetic origins.A total 103 patients with either CPHD (n = 35) or 68) were investigated for mutations genes implicated etiology KS (FGFR1, FGF8, PROKR2, PROK2, KAL1). Consequences identified FGFR1, PROKR2 vitro.Three had heterozygous FGFR1;...