Endocrine Abstracts

Congenital adrenal hyperplasia (CAH) is one of the most common inherited disorders. The majority of CAH cases are due to 21-hydroxylase deficiency (21-OHD) caused by mutations in CYP21A2. Because of the profound impact of steroids on physiology and gene expression, the imbalances in steroid hormones resulting from 21-OHD are supposedly leading to a whole-organism response on transcriptome and metabolome level. The systemic consequences of severe 21-OHD during early development...

Steroid hormones are important regulators of many physiological processes. The steroid precursor pregnenolone is converted through several enzymatic steps into all types of steroids, including the stress hormone cortisol. Mitochondrial steroidogenic cytochrome P450 (CYP) enzymes crucially relying on electron transfer from the redox partner ferredoxin (FDX1) are involved in key steps of the cortisol biosynthesis pathway.Cortisol is well-known regulator of...

NAD+, an essential coenzyme in energy production, has recently risen to prominence as a signalling molecule central in mediating cellular metabolism and mitochondrial function. NAD+ dependent protein deacetylase sirtuin (SIRT) proteins regulate key metabolic transcription factors, including FOXOs and PGC-1α in muscle, in response to cellular energy demands and metabolic stress. Declining NAD+, metabolic and mitochondrial function are hallm...

Mitochondrial steroidogenic cytochrome P450 (CYP) enzymes, such as P450 side-chain cleavage, rely on electron transfer from the redox partner ferredoxin (FDX1) for catalytic activity. Previous in vitro data suggest these cofactors are key regulators of CYP enzyme activity. This study aims to establish the role of redox regulation on steroidogenesis using zebrafish as a vertebrate in vivo model.In contrast to humans, zebrafish have two F...

Zebrafish has emerged as an important vertebrate in vivo model to study human disease. Steroidogenesis in zebrafish is not well characterised. Human CYP11A1 (hCYP11A1) catalyses the first step of steroidogenesis, the conversion of cholesterol to pregnenolone. Zebrafish Cyp11a1 (zCyp11a1) is essential during embryogenesis. Published data suggest that zCyp11a1 facilitates steroidogenesis in the interrenal (equivalent to mammalian adrenal), gonad and brain. We identified...

Cytochrome P450 side-chain cleavage enzyme (CYP11A1) catalyses the first and rate-limiting step of steroidogenesis. CYP11A1 firstly converts cholesterol into 22R-hydroxycholesterol, which relies on mitochondrial steroidogenic acute regulatory protein (StAR)-mediated cholesterol import. Two further StAR-independent CYP11A1 reactions facilitate pregnenolone biosynthesis. CYP11A1 deficiency is rare and manifests with adrenal insufficiency (AI), and, in 46,XY individuals, with nor...