The importance of dynamic signalling for endocrine regulation and drug development: relevance for glucocorticoid hormones

Glucocorticoid hormones are heavily prescribed for several indications, including hormone replacement, anti-inflammatory effects, and antineoplastic effects. The pharmaceutical industry has put much effort into the development of novel potent glucocorticoid agonists, whereas there has been little enthusiasm for development of temporal aspects of glucocorticoid drugs. Glucocorticoids are normally secreted in a highly dynamic fashion, not only in the well known 24 h circadian rhythm, but also in an approximately hourly ultradian rhythm. These rhythms are crucial for normal gene regulation and for optimum cognitive function. In this Personal View, we discuss how understanding normal oscillatory patterns of glucocorticoid secretion could help investigators to develop novel glucocorticoid therapeutics that maximise the beneficial effect and diminish unwanted side-effects.