Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn

Research

Background

Steroid hormones affect a wide variety of cellular processes ranging from whole body electrolyte and fluid balance, cell excitability, metabolism, proliferation and differentiation. These effects occurring over hours to days are genomic involving transcription and translation, new protein synthesis and are initiated by steroid binding to a nuclear receptor. In recent years more than 300 refereed papers have appeared for all steroid hormones describing their ability to activate signal transduction pathways which rapidly (seconds to minutes) lead to a variety of biological responses. Increasing evidence is being accumulated for rapid physiological steroid responses in humans, e.g. at the level of electrolyte and fluid homeostasis and circulatory or metabolic effects, rendering clinical significance to rapid responses to steroid hormones (RRSH).

Objectives

The major objective of our research programme is to uncover the physiological role of rapid responses for the steroid hormones aldosterone, glucocorticoids and estrogen in epithelial tissues of the intestine, lung and kidney. Specifically, we investigate the functions of novel receptors and interacting proteins for these hormones, their signal transduction pathways and their membrane targets. A major objective is to understand the impact of the rapid responses to steroid hormones on the genomic phase and their role in disease states such as cystic fibrosis, hypertension, cancer and inflammation. We postulate the end result of the RRSH pathway for these hormones in pluripotential epithelia such as the intestine and lung is to shift the balance from net secretion to net fluid and electrolyte absorption.