You are here:
Hormone action
The function of every tissue in the body is controlled by a vast array of hormones, growth factors and other signalling molecules.
They bind to receptor proteins in cells that make up tissues and trigger alterations in genetic activity. While all cells contain an identical repertoire of approximately 30,000 genes they are not all expressed and each type of cell expresses distinct subsets responsible for their individual functions.
The initial focus of Malcolm’s research was to understand how steroid hormones like oestrogen and testosterone regulate the growth of breast and prostate cancers. During the course of this work we discovered certain genes that make proteins with a completely novel function – cofactors for nuclear receptors. Amazingly, while we estimate that there are about 30,000 protein coding genes in the human genome essentially nothing is known about the function of more than half of them and Professor Parker’s lab has spent the last 15 years working out the function of these cofactors in reproduction, inflammation and metabolism.
The background to our discovery is as follows. It’s been known for decades that steroid hormones bind to specific receptors inside cells. As the levels of different hormones fluctuate, for example during the female cycle or after exercise or stressful circumstances, individual receptors are switched on. As a consequence, the activity of different subsets of genes are regulated. Some genes are activated, some repressed, depending on the recruitment of proteins called coactivators and corepressers that change genetic function. Amongst the first of this new type of cofactor was one we discovered and called RIP140, short for receptor interacting protein, in 1995. Five years later we showed it is essential for female fertility. Subsequent studies revealed that it was necessary for ovulation because it promotes the signal that prepares cumulus cells surrounding the oocyte or egg. It is also crucial for determining the amount of fat we store in adipose tissues and also plays a role in inflammation. Thus RIP140 has various functions important for infertility, and in obesity, diabetes and inflammation.