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Molecular Medicine

Molecular Medicine Research Thematic

Steroid hormones such as mineralocorticoids, glucocorticoids and sex steroids affect a wide variety of biological processes ranging from whole body electrolyte and fluid balance, cellular excitability, proliferation and differentiation. These effects occur over hours to days and are genomic involving new protein synthesis and are initiated by steroid binding to a nuclear receptor. Over the past decade, evidence has accumulated for a more rapid steroid hormone response (seconds-minutes) that involves novel membrane-associated receptors and nongenomic activation of signal transduction pathways. Rapid physiological steroid responses occur in humans, e.g. at the level of electrolyte and fluid homeostasis, cell proliferation and circulatory or metabolic effects, rendering clinical significance to these rapid responses to steroid hormones (RRSH). The objective of our research is to provide an integrated understanding of rapid responses for the steroid hormones aldosterone, glucocorticoids and estrogen in epithelial tissues of the intestine, lung and kidney. Specifically, we will determine novel receptors and interacting proteins for these hormones, their cellular signal transduction pathways, and their membrane transporter targets (ion channels, pumps and exchangers) and the impact of the rapid responses on whole tissue/organ physiology and on the slower genomic phase. 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. Thus the programme has high relevance to treatment of disease states of electrolyte and fluid imbalances such as hypertension and secretory diarrhoea.

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