Endocrine Abstracts

11β-hydoxysteroid dehydrogenase type 1 (11β-HSD1) essentially catalyzes the conversion of the inactive endogenous glucocorticoid cortisone (11-dehydrocorticosterone in rodents) and the synthetic prednisone into the active cortisol (corticosterone in rodents) and prednisolone. The association of an elevated expression of 11β-HSD1 with metabolic disease has been extensively studied in humans and in rodent models. It is generally assumed that the effects that are o...

Membrane proteins of the endoplasmic reticulum (ER) are involved in a wide array of essential cellular functions. Identification of the topology of membrane proteins can provide important insight into their mechanisms of action and biological roles. This is particularly important for membrane enzymes, since their topology determines the subcellular site where a biochemical reaction takes place and the dependence on luminal or cytosolic substrates and co-factor pools. The metho...

Mammalian Leydig cells produce the majority of the systemic levels of the primary male sex hormone testosterone. Testosterone plays a crucial role during development of male reproductive tissues, onset of puberty, and maintaining health state. The final step of testosterone synthesis is catalyzed by 17β-hydroxysteroid dehydrogenase 3 (17β-HSD3). Disruption of testosterone synthesis is associated with many diseases. Due to the lack of a human Leydig cell line, two dif...

Impaired 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2)-dependent cortisol inactivation can lead to electrolyte dysbalance, hypertension and cardiometabolic disease. Furthermore, placental 11β-HSD2 essentially protects the fetus from high maternal glucocorticoid levels, and its impaired function has been associated with altered fetal growth and a higher risk for cardio-metabolic diseases in later life. Despite its important role, 11β-HSD2 is not include...

Disruption of the gut-liver axis contributes to metabolic syndrome and the progression of non-alcoholic fatty liver disease (NAFLD). Bile acids (BAs) are potent antimicrobials that support gastrointestinal health and dysregulation of BA homeostasis in NAFLD is thought to contribute to gut dysbiosis. Furthermore, an increase in hydrophobic (cytotoxic) BA species may directly affect gut health. We have previously shown that bile acid synthesis enzyme, 5β-reductase (AKR1D1),...

Steroid hormones and bile acids are potent regulators of metabolic phenotype. The enzyme 5β-Reductase (AKR1D1) has a crucial role in bile acid synthesis and also generates 5β-reduced dihydrosteroid metabolites, regulating intra-cellular steroid availability though the clearance of cortisol, testosterone, androstenedione and progesterone. As AKR1D1 sits at the interface of bile acid synthesis and steroid metabolism, we have hypothesised that it plays a key role in met...

Steroid hormones and bile acids are potent regulators of metabolic phenotype. The enzyme 5β-reductase (AKR1D1) has a crucial role in bile acid synthesis and also generates 5β-reduced dihydrosteroid metabolites, regulating intra-cellular steroid availability though the clearance of cortisol, testosterone, androstenedione, and progesterone. As AKR1D1 sits at the interface of bile acid synthesis and steroid metabolism, we have hypothesised that it plays a key role in me...

Metabolic syndrome (MS) is an important etiologic risk factor for the development and progression of certain cancers, including colorectal. Bile acids (BA) are potent antimicrobials that support gastrointestinal health and the dysregulation of BA homeostasis is thought to contribute to gut dysbiosis and drive endotoxemia. Furthermore, an increase in the cytotoxicity ofintestinal BA species can directly damage enterocytes and promote carcinogenesis. We have previously shown tha...

Steroid hormones and bile acids are potent regulators of metabolism. The enzyme 5β-reductase (AKR1D1) has a crucial role in bile acid synthesis and also generates 5β-reduced dihydrosteroid metabolites, regulating intra-cellular steroid availability though the clearance of cortisol, testosterone, androstenedione, and progesterone. As AKR1D1 sits at the interface of bile acid synthesis and steroid metabolism, we have hypothesised that it plays a key role in metabolic h...

Human adrenal H295R cells are applied according to the validated OECD test guideline 456 to identify potential endocrine disrupting chemicals. Testosterone and estradiol production serves as read-out although these are not steroids typically produced by the adrenals. The current study attempted to optimize conditions for using H295R cells to detect chemicals disturbing the synthesis of key adrenal steroids. Culture supernatants of H295R cells were analysed by LC-MS-based stero...