Matthews - glucocorticoids and the epigenome

We’ve been very interested in how glucocorticoids interact with the developing epigenome. And so other studies in our lab have been looking to see what the acute effects of glucocorticoids are on the fetal epigenome, and we’ve been focused very much on the hippocampus. The hippocampus is a part of the brain that’s critical in learning and memory, it’s critical in many functions. But it’s also very important in actually modulating the activity of the hypothalamic pituitary adrenal axis, the stress axis. And so, we focused initially on the hippocampus, but we are looking elsewhere as well within that pituitary adrenal axis. But what we’re discovering is that glucocorticoids do have a major impact on the developing epigenome. We’ve shown that these effects last for a substantial amount of time; that they last into the perinatal period. And we’re starting to see effects also in adulthood following this prenatal exposure to glucocorticoid. So then we’re starting to get a handle on some of the mechanisms.  

But one of the things that, then in all of our work that’s become clearer and clearer is just the ability or the plasticity of the hypothalamic pituitary adrenal axis, or this HPA or stress axis. That the early environment, particularly the fetal environment, can have a huge impact on how that system operates throughout the life of that individual, be it human or an animal. And, really, this is a fundamental system; this is not only the system that regulates your responsiveness to stress, but the HPA axis and cortisol particularly, is essentially critical throughout life, in maintaining resource allocation. And, so it’s very important in regulating metabolism, has important roles in reproduction, everything to do with resource allocation within an individual, glucocorticoids are involved. And, so this is really, sort of, coming to the other the other side of it. So we know that glucocorticoids are very important in programming the developing brain. We know that exposure, early exposure to glucocorticoids can have programming effects on that individual’s pituitary adrenal axis, so that individual’s pituitary adrenal axis is, has altered function throughout life. And we know that pituitary adrenal function is critical in development of, or susceptibility to a number of diseases; a number of cardio metabolic diseases and a number of neurological disorders have been linked to inappropriate cortisol regulation.