Endocrine Abstracts

Without adequate treatment patients with acromegaly die prematurely from cardiovascular disease (CVD); however the contribution of atherosclerosis in this process is controversial. Increased carotid IMT is an early morphological marker of atherosclerosis and predictor of subsequent cardiovascular events. Contradictory data exist regarding IMT in patients with acromegaly.We measured carotid IMT in 79 patients with acromegaly (47 male, mean age 55±14 ...

Background: 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 individua...

We have recently identified inactivating mutations in the electron donor enzyme P450 oxidoreductase as the cause of disease in patients with apparent combined P450c17 and P450c21 deficiency, a variant of congenital adrenal hyperplasia (CAH) (1). Additionally, we suggested that P450 oxidoreductase deficiency (ORD) reveals the existence of an alternative pathway in human androgen synthesis present in fetal life only, explaining the concurrent presence of low circulating androgen...

Androgen excess is a key feature of the polycystic ovary syndrome; however the molecular mechanisms underlying its pathogenesis largely remain elusive. Dehydroepiandrosterone sulfate (DHEAS) is the most abundant steroid in the human circulation but only unconjugated dehydroepiandrosterone (DHEA) can be converted to active androgens. Conversely, conversion of DHEA to its sulfate ester DHEAS by DHEA sulfotransferase, SULT2A1, diminishes the DHEA pool available for androgen gener...

Steroid 17α-hydroxylase (CYP17A1) deficiency (17OHD) is a rare form of congenital adrenal hyperplasia (CAH). Both, 17-hydroxylase and 17,20-lyase reactions are catalysed by CYP17A1. Here, we analysed the structural and functional consequences of 3 novel CYP17A1 mutations found in 3 patients suffering from 17OHD. Two individuals with 46,XY DSD, presented with tall stature and one with arterial hypertension. Mutation screening of the CYP17A1 gene revealed comp...