Searchable abstracts of presentations at key conferences in endocrinology

ea0013oc7 | Society for Endocrinology/Clinical Endocrinology Trust Young Investigator Basic Prize winner | SFEBES2007

Differential effects of P450 oxidoreductase mutants on CYP17 activity provides evidence for an alternative pathway in human androgen biosynthesis

Dhir Vivek , Ivison Hannah E , Krone Nils , Stewart Paul M , Shackleton Cedric HL , Arlt Wiebke

Congenital adrenal hyperplasia (CAH) caused by mutations in the electron donor enzyme P450 oxidoreductase (POR) is unique amongst all CAH variants in that it can be associated with ambiguous genitalia (disordered sex differentiation, DSD) both in 46,XX and 46,XY individuals. POR has a pivotal role in facilitating electron transfer from NADPH to microsomal P450 enzymes, including CYP17, which catalyses a key step in human androgen synthesis, the conversion of 17-hydroxypregneno...

ea0012s14 | New frontiers in steroid hormone metabolism | SFE2006

P450 oxidoreductase and androgen metabolism

Dhir Vivek , Krone Nils , Ivison Hannah E , Stewart Paul M , Shackleton Cedric HL , Arlt Wiebke

P450 oxidoreductase (POR) has a pivotal role as electron donor to all cytochrome P450 enzymes that are microsomally located, i.e. CYP type II enzymes. Importantly, those include key enzymes involved in glucocorticoid and sex steroid biosynthesis such as CYP17 and CYP21. In addition, the activity of hepatic CYP enzymes involved in drug metabolism and detoxification also crucially depend on the transfer of electrons from NADPH via POR. Recently, mutations in P450 oxidoreductase ...

ea0015p331 | Steroids | SFEBES2008

Early truncation of the human CYP17A1 protein results in severe neonatal adrenal insufficiency

Ivison Hannah E , Shenoy Savitha , Arlt Felix J , Krone Nils , Shackleton Cedric HL , Taylor Norman F , Arlt Wiebke

CYP17A1 is a key enzyme of human steroidogenesis, which is unique in that it catalyses two reactions, 17-hydroxylase activity converting pregnenolone and progesterone to 17-hydroxypregnenolone (17Preg) and 17-hydroxy-progesterone, respectively, and 17,20 lyase activity, responsible for the conversion of 17Preg to dehydroepiandrosterone the crucial precursor of human sex steroid biosynthesis. 17-hydroxylase deficiency, a variant of congenital adrenal hyperplasia, results in glu...

ea0015oc16 | Reproduction | SFEBES2008

Enhanced hypothalamic–pituitary–adrenal axis activation, 5α-reductase activity and insulin resistance distinguishes polycystic ovary syndrome from simple obesity

Vassiliadi Dimitra A , Tomlinson Jeremy W , Hughes Beverly A , Gay Christopher , Sira Shaleen , Nightingale Peter , Shackleton Cedric HL , Stewart Paul M , Arlt Wiebke

Polycystic ovary syndrome (PCOS) affects 5–10% of the female population. It is characterised by androgen excess and anovulatory infertility; several studies have reported an increased incidence of the metabolic syndrome and enhanced 5α-reductase activity in PCOS. However, the contribution of obesity to these findings has yet to be clarified. Here we have analysed metabolic status and urinary steroid metabolite excretion in 114 patients with PCOS (median age 30 (range...

ea0063oc10.1 | Adrenal 2 | ECE2019

Steroid metabolomics: a rapid computational approach for accurate differentiation of inborn disorders of steroidogenesis

Baranowski Elizabeth S , Ghosh Sreejita , Shackleton Cedric HL , Taylor Angela E , Hughes Beverly A , Gilligan Lorna C , Utari Agustini , Faradz Sultana MH , van Herwaarden Antonius E , Claahsen-van der Grinten Hedi L , Biehl Michael , Guran Tulay , Bunte Kerstin , Tino Peter , Arlt Wiebke

Background: Measurement of steroid metabolite excretion in urine by gas chromatography-mass spectrometry (GC-MS) provides a comprehensive profile of an individual’s adrenal and gonadal steroid production. It has long been acknowledged as a useful tool for diagnosis of inborn disorders of steroidogenesis leading to congenital adrenal hyperplasia and disorders of sex development. Ratios of steroid metabolites can be employed as surrogates for enzymatic activities of distinc...