Hormone resistance of pituitary tumors and Cushing disease explained

Montréal scientists led by Dr Jacques Drouin, researcher at the Institut de recherches cliniques de Montréal (IRCM), and collaborators from around the world (Canada, France, the Netherlands and United States) unravel mechanism of hormone resistance in pituitary tumors of Cushing disease patients.

Cushing disease is caused by pituitary tumors that produce excessive amounts of hormone because the tumor cells have become resistant to negative feedback control by a class of steroid hormones, glucocorticoids. In Cushing disease, this excessive hormone production can lead to hypertension, obesity, diabetes and osteoporosis. Through detailed molecular investigation of the mechanism of this negative feedback, a Montréal research group has identified two essential components (proteins) of this feedback mechanism. Extrapolating from these basic studies, they have shown that about half of the pituitary tumors from Cushing disease patients are deficient in expression of either of these proteins, thus providing a molecular explanation for the hormone resistance that is the hallmark, and likely first event, in the formation of these tumors. The novel insight provided by knowledge of the basic mechanism of hormone resistance will lead to the rational design of therapeutic approaches for the better management of Cushing disease patients. This insight will also help understand other forms of hormone resistant cancers.

Dr. Jacques Drouin is the Director of the Molecular Genetics Research Unit at IRCM. He holds the GlaxoSmithKline Chair in Molecular Genetics. The IRCM (www.ircm.qc.ca) is recognized as one of the country's top-performing research centres. It has a mandate to establish links between research and patients, promote the prevention of illness, and train a new generation of high-level scientists. The IRCM has 37 research units and a staff of more than 450. The IRCM is also affiliated to Université de Montréal.

This work is published in Genes and Development (Bilodeau et al, Genes Dev 2006, 20:2871-2886) and it was supported by grants from the Canadian Cancer Society and from the Canadian Institutes of Health Research.