Endocrine Abstracts

The endogenous decarboxylated thyroid hormone (TH) metabolite 3-Iodothyronamine (3-T1AM) exerts partially TH antagonistic effects in rodents and was shown to suppress the hypothalamic pituitary thyroid axis in rats after single dose application. Therefore, it might play a role in maintaining TH homoeostasis. Among the molecular targets of 3-T1AM are G protein-coupled receptors like the trace amine associated receptor 1 (TAAR1) and adrenergic receptors. Furthermore, 3-T1AM was ...

The function of the thyroid gland is to maintain thyroid hormone (TH) levels in the blood circulation. Thyroid epithelial cells liberate TH from the precursor molecule thyroglobulin (Tg) by the combined proteolytic action of the cathepsin B, K, L, and S. Cathepsin L-deficiency in mice results in impaired processing of Tg and remnants of dead cells in the follicle lumen. Recently, we have shown that Trace amine-associated receptor 1 (Taar1) is localized on the primary cilia of ...

In a previous study we found mutations in the main catalytic subunit of protein kinase A (PKA Cα) to be responsible for cortisol-secreting adrenocortical adenomas (ACAs). These mutations interfere with the formation of a stable holoenzyme, thus causing constitutive PKA activation. More recently, we identified additional mutations affecting PKA Cα in ACAs associated with overt Cushing syndrome: Ser213Arg_Leu212_Lys214insIle-Ile-Leu-Arg, Cys200_Gly201insVal, Trp197Arg,...

The cyclic AMP/PKA signalling cascade and PKA subunits are involved in the pathogenesis of a subset of cortisol-secreting adrenocortical tumors (ACT). In addition, steroid excess causes morbidity of all types of ACT.The PKA regulatory subunits PRKARIA, PRKARIIb control proliferation/apoptosis in the H295R adrenocortical cell line. Their inactivation enhances the accumulation of cells in the G2 phase, increases steroidogenesis and activa...

Glucocorticoids (GC) are critical to stress adaptation but in excess (Cushing’s syndrome) drive metabolic dysfunction. 11β-hydroxysteroid dehydrogenase type 1(11β-HSD1) amplifies intracellular GC signaling with 11β-HSD1KO mice protected from the side-effects of GC excess. Brown adipose tissue (BAT) function is impaired by GC’s, which repress UCP1 and beta-adrenergic stimulated thermogenesis. Identifying mechanisms regulating BAT function is important a...