Abstract

Steroid Homeostasis and Clinical Mass Spectrometry; Moving Beyond Concentration

Ruth Andrew, Reader, Edinburgh University

Routine clinical biochemical analysis of steroid hormones is moving towards the application of tandem mass spectrometry, interfaced with both liquid and gas chromatography, offering enhanced specificity over immunoassays. Clinically, circulating steroids are used to capture information on the amount of steroid hormone available for endocrine signalling. However it is increasingly recognised that steroids are interconverted between their inert and active states within tissues e.g. by enzymes such as aromatase, 11?-hydroxysteroid dehydrogenase type 1 or 5?-reductases. These enzymes modulate "intracrine" actions of the hormones and their roles in disease cannot be assessed from measurement of plasma concentrations of hormone alone. Interest in intracrinology has driven forward innovative ways of measuring steroid metabolism within tissues e.g. in adipose and liver in type 2 diabetic subjects. We have developed approaches to quantify glucocorticoid synthesis by metabolic tissues using stable-isotope labelled steroids, in conjunction with arterio-venous sampling and more recently applied this in conjunction with matrix assisted laser desorption ionisation-Fourier transform ion cyclotron resonance mass spectrometry imaging to profiling active hormone and inert metabolites in tissue sections. These approaches allow rates of steroid synthesis within tissues and functional sub-regions to be assessed, offering greater insight into regional pathology and responses to steroid synthesis inhibitors.