Endocrine Abstracts

In humans, androgen synthesis crucially depends on the enzyme CYP17A1 expressed in adrenals and gonads. The 17,20 lyase activity of CYP17A1 catalyses the key step in human androgen biosynthesis, the conversion of 17-hydroxypregnenolone to the universal sex steroid precursor dehydroepiandrosterone (DHEA). For its catalytic activity, CYP17A1 requires electron transfer from P450 oxidoreductase (POR). Mutations in CYP17A1 and POR are known to disrupt human androgen s...

Rheumatoid arthritis (RA) is associated with a loss of lean mass and a corresponding increase in fat mass. How fat accumulation in RA is linked to synovial inflammation is unknown. Wnts comprise a family of secreted glycoproteins that are crucial in regulating adipocyte proliferation, apoptosis and differentiation. Recently we demonstrated that endogenously generated glucocorticoids (GCs) alter the pattern of wnt secretion by synovial fibroblasts (SFs), favouring production of...

Synovial fibroblasts (SFs) form a substantial component of inflamed rheumatoid synovium and generate endogenous glucocorticoids (GCs) during inflammation. Recently, production of DKK-1 (a Wnt signalling inhibitor that reduces bone formation) by SFs in response to TNFα has been proposed to be the master regulator of inflammatory osteoporosis. We have identified that in addition to TNFα, GCs potently induce DKK-1 secretion. This may provide a novel mechanism whereby lo...

Steroid 17α-hydroxylase (CYP17A1) exerts two distinct activities that catalyze conversion reactions at key branch points in steroidogenesis. CYP17A1 17α-hydroxylase activity is the key step in cortisol synthesis whereas CYP17A1 17,20 lyase activity generates sex steroid precursors. Inactivating CYP17A1 mutations result in CYP17A1 deficiency (17OHD), a rare form of congenital adrenal hyperplasia that classically presents with combined glucocorticoid and sex steroid de...