Endocrine Abstracts

Adrenal-derived glucocorticoids originate from their precursor cholesterol. Scavenger receptor BI (SR-BI) is a major high-density lipoprotein (HDL) receptor that mediates the selective uptake of cholesteryl esters (CE) from this lipoprotein in the circulation. In our present studies in SR-BI knockout (KO) mice and human carriers of a functional mutation in the extracellular domain of SR-BI (P297S), we determined whether SR-BI-mediated uptake of HDL-CE is required for adrenal g...

Urocortin 2 (Ucn2) is a recently identified neuropeptide of the CRF-Family, involved in homeostatic mechanisms for stress response and control of anxiety. To further elucidate Ucn2 effects on steroidogenesis, we developed a mouse model with Ucn2 overexpression in the adrenals, gonads and parts of the hypothalamus, by crossbreeding SF1-Cre+/− mice with R26stop UCN2/stop UCN2 mice. Following genotypes were obtained: SF1-Cre&...

Membrane expression of ACTH receptor MC2R is specifically limited to adrenal cells. In addition, unlike the other members of the evolutionary related MCRs that recognize different melanocortin peptides, the MC2R solely binds ACTH. We used cassette substitutions and mutagenesis of individual amino acids for systematic construction of 30 chimeric and mutant MC2R/MC4R receptors to identify the receptor structures determining the selectivity of MC2R in membrane trafficking and ACT...

Introduction: ACTH stimulates adrenocortical steroid production through the melanocortin 2 receptor (MC2R). MC2R trafficking and signaling depend on the melanocortin 2 receptor accessory protein (MRAP). The MRAP-homolog MRAP2 also transports the MC2R but prevents effective activation. We investigated expression of these components of the MC2R complex in human adrenal tissues in order to uncover novel regulatory mechanisms and their contribution to ACTH responsiveness.<p cl...

Introduction: The biological activity of thyroid hormone (TH) is largely mediated by binding of T3 to nuclear T3 receptors (TRs). Before TH can mediate its effects, it needs to be transported across the plasma membrane. Several TH transporters, such as MCT8, facilitate this transport. Inactivating mutations in MCT8 lead to a severe phenotype of psychomotor retardation. In addition to transport into the cell, MCT8 is also able to transport TH out of the ce...

Enzymatic 5′- and 5-deiodination represent key pathways for local and systemic and local activation and inactivation of iodothyronines and iodothyronamines. Expression of the three respective deiodinases (DIO) is regulated by thyroid parameters, local and systemic inflammatory status as well as by selenium supply. In addition, the DIO isoenzymes are intended but also unanticipated target proteins of pharmacological, nutritive and environmental substances that might inter...