Searchable abstracts of presentations at key conferences in endocrinology

ea0028oc1.7 | Young Endocrinologists prize session | SFEBES2012

Progressive adrenal insufficiency and 46,XY DSD caused by two novel mutations in the cytochrome P450 side-chain cleavage (CYP11A1) gene

Parajes Silvia , Chan Angel , But Betty , Rose Ian , Taylor Angela , Griffin Aliesha , Dhir Vivek , Arlt Wiebke , Krone Nils

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...

ea0025oc2.5 | Steroids | SFEBES2011

A novel entity of isolated adrenal insufficiency caused by partial inactivation of P450 side-chain cleavage (CYP11A1) enzyme

Parajes Silvia , Kamrath Clemens , Rose Ian , Taylor Angela , Mooij Christiaan , Dhir Vivek , Grotzinger Joachim , Arlt Wiebke , Krone Nils

Cytochrome P450 side-chain cleavage enzyme (CYP11A1) catalyses the first and rate-limiting step of steroidogenesis, facilitating conversion of cholesterol to pregnenolone. Cholesterol, transported by steroidogenic acute regulatory protein (StAR) into the inner mitochondrial membrane, is converted by CYP11A1 into 22R-hydroxycholesterol. Subsequently, CYP11A1 converts 22R-hydroxycholesterol by 20alpha-hydroxylation and cleavage of the C20–C22 bond into pregnenolone. All pat...

ea0037gp.05.02 | Developmental and paediatric endocrinology | ECE2015

The differential impact of PAPS synthase isoforms on DHEAS may be explained by an isoform-specific interaction of SULT2A1 with PAPSS2, but not PAPSS1

Mueller Jon W , Idkowiak Jan , Hardman Rebecca E , House Philip J , McNelis Joanne C , Rose Ian T , Dhir Vivek , Rosta Edina , Arlt Wiebke

Human sulfation depends on provision of the universal sulfate donor PAPS by the two PAPS synthase isoforms PAPSS1 and PAPSS2. Mutations in PAPSS2 have been identified as a monogenic cause of androgen excess presenting with premature adrenarche and polycystic ovary syndrome, due to decreased sulfation of the androgen precursor DHEA by DHEA sulfotransferase (SULT2A1) and hence increased conversion of DHEA to active androgens (New Eng J Med 2009 360 (22)...

ea0034p374 | Steroids | SFEBES2014

Differential impact of PAPS synthases on human sulfation pathways

Mueller Jonathan W , Idkowiak Jan , House Philip J , McNelis Joane , Rose Ian I , van den Boom Johannes , Schlereth Florian , Dhir Vivek , Arlt Wiebke

Mutations in the gene for 3′-phospho-adenosine-5′-phosphosulfate synthase 2 (PAPSS2) are linked to bone and cartilage mal-formation. More recently, we could identify PAPSS2-mutations as mono-genetic cause for androgen excess in women due to apparent SULT2A1 deficiency, the enzyme responsible for sulfation of the testosterone precursor DHEA that relies on PAPS provision by PAPS synthases. The only human orthologue, PAPSS1, is expressed in the affected tissu...

ea0028p306 | Steroids | SFEBES2012

Genotype-phenotype correlation in 153 adult patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency - analysis of the United Kingdom Congenital adrenal Hyperplasia Adult Study Executive (CaHASE) cohort

Krone Nils , Rose Ian , Willis Debbie , Wild Sarah , Hodson James , Doherty Emma , Hahner Stefanie , Parajes Silvia , Stimson Roland , Han Thang , Carroll Paul , Conway Gerard , Walker Brian , Macdonald Fiona , Ross Richard , Arlt Wiebke , CaHASE The UK CAH Adult Study Executive

In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency a genotype-phenotype correlation exists for paediatric cohorts, helping to predict the severity of disease expression. Data on the correlation in adults is lacking. Here we report the genetic analysis of the UK CaHASE cohort, comprising CAH adults seen at 17 endocrine tertiary care centres. CYP21A2 mutation analysis was performed in 153 patients (median age 35 (range 18–69) yrs; 103 f, 50 m) by multi...