Endocrine Abstracts

Background: Adrenocortical carcinoma (ACC) is a very rare and aggressive, endocrine malignancy with still limited treatment options. Approximately 60% of patients with ACC show endogenous glucocorticoid excess which could be one potential cause, why first clinical trials with immunotherapies, like immune checkpoint inhibitors, showed only modest results. Due to the lack of an ACC-specific antigen structure, other immunotherapeutic approaches, like specialized cancer treatments...

The Mineralocorticoid Receptor (MR, NR3C2) mediates sodium-retaining action of aldosterone. Recently, we have shown that the physiological sodium loss observed in newborns in their first days of life is due to a low renal MR expression. However, the underlying molecular mechanisms remain unknown to date. In the adult renal KC3AC1 cell line, we demonstrated that variations in extracellular tonicity, which exist in the nephron, modulate MR expression by posttranscriptio...

Background: Men with obesity often have low total and, with increasing adiposity, also free testosterone (T) levels, which can partially restore when they lose weight. Although this is in part explained by lower sex-hormone binding globulin (SHBG) production and hypothalamic-pituitary downregulation, it is still not fully unraveled whether changes in androgen metabolization contribute to this phenomenon.Aim: Investigating metabolisation of sex steroids d...

The 11-beta hydroxysteroid dehydrogenase (11βHSD) isozymes are well-known regulators of glucocorticoid hormone metabolism: 11βHSD2, mostly expressed in the distal nephron, converts cortisol [F] into cortisone [E] in humans or corticosterone into 11-dehydrocorticosterone in rodents (11-dehydro derivatives being inactive compounds), and 11βHSD1, ubiquitously expressed but predominantly in the liver, catalyzes the opposite reaction. Under pathophysiological conditi...

The leptin/melanocortin pathway plays a critical role in hypothalamic control of food intake. Variants in the genes involved in this pathway, such as leptin (LEP), its receptor (LEPR), proopiomelanocortin (POMC) or proconvertase 1 (PCSK1) are associated with early-onset severe obesity and endocrine abnormalities especially in case of homozygosity. Heterozygous variants in the melanocortin-4 receptor (MC4R) gene are associated with an increased risk of severe obesity. The aim i...

Background: Men with obesity often have low total and, with increasing adiposity, also free testosterone (T) levels, which can partially restore when they lose weight. Although this is in part explained by lower sex-hormone binding globulin (SHBG) production and hypothalamic-pituitary downregulation, it is still not fully unraveled whether changes in androgen metabolization contribute to this phenomenon.Aim: Investigating metabolisation of sex steroids d...

Primary generalized glucocorticoid resistance is characterized by glucocorticoid excess without any Cushing syndrome. Patients exhibit variable clinical presentation including arterial hypertension, hirsutism or adrenal hyperplasia. Although glucocorticoid resistance has been associated with glucocorticoid receptor (GR) mutations (encoded by NR3C1 gene), only 23 mutations have been reported so far. We have conducted a French National Research Program, referred to as M...

The anti-fibrotic, vasodilatory, and angiogenic therapeutic properties of relaxin peptide have been shown in several animal models of human diseases and in clinical trials. Using high-throughput screening of small molecule library, structure-activity relationship (SAR) studies, ligand-receptor interaction modeling, site-specific mutagenesis, and transgenic animal studies we discovered the first series of small molecule agonists of relaxin GPCR, RXFP1. The lead compound ML290 i...

Introduction: Glucose-dependent insulinotropic peptide (GIP) induces the cytokine interleukin (IL)-6 in adipocytes. IL-6 enhances insulin secretion from β-cells via L- and α-cell-derived GLP-1.Therefore we hypothesized that GIP regulates Glucagon-like peptide (GLP)-1 as well as glucose control via IL-6.Methods/Design: Basic research study on isolated human and mouse pancreatic islets and FACS-sorted human α-and β-cells that were treat...

Tumor-induced osteomalacia (TIO) is a rare acquired paraneoplastic syndrome clinically presenting with recurring fractures, muscular weakness and pain. Laboratory values of affected patients are characterized by renal phosphate wasting and hypophosphatemia caused by an overexpression of fibroblast growth factor 23 (FGF- 23), a hormone belonging to the group of phosphatonins regulating phosphate and vitamin D homeostasis. Pathologically, it is secreted especially by small (and ...