GROUP LEADER: Prof. Ann Louw
Office: A119 JC Smuts Building
PhD, University of Stellenbosch, Biochemistry, 1998
NRF C2-rating (2013-2018)
Golden Key International Honour Society Award for Best lecturer in Science Faculty (2008)
Steroid receptor signal transduction, Steroid-binding globulins, Phytoestrogens, Dissociated glucocorticoids, Interplay of stress and immune function.
Our research focus is on steroid hormone binding proteins, specifically the steroid hormone transport proteins in serum and intracellular steroid hormone receptors. The interplay between these two categories of steroid hormone binding proteins, whether elicited by drugs or physiological conditions, has been neglected in an era of specialization despite the obvious physiological relevance.
We aim to study the effects of specific compounds, such as Compound A and phytoestrogens, or physiological conditions, such as stress, on steroid hormone signal transduction via cognate receptors, such as the glucocorticoid receptor (GR) and oestrogen receptor (ER). This is complemented by investigating effects on the high affinity steroid binding globulins, specifically corticosteroid binding globulin (CBG) and sex hormone binding globulin (SHBG).
Molecular mechanism of action of GR – focus on implications of dimerization
Glucocorticoids remain the most effective treatment for inflammatory diseases. However, side-effects limit their usefulness. Dissociated glucocorticoids, which discriminate between transactivation and transrepression, have recently been hailed as drugs that retain potent anti-inflammatory action while displaying reduced side-effects. Compound A, synthesized in our department, is such a dissociated glucocorticoid and may exert its dissociated activity through abrogation of GR dimerization. We are currently investigating the implications of a gain or loss of dimerization potential on the biological action of GR.
Phytoestrogenic activity of Cyclopia (honeybush)
Alternatives for hormone replacement therapy are avidly sought and phytoestrogens have been hailed as a viable alternative with fewer side-effects. We have established that Cyclopia contains phytoestrogens and that an extract from Cyclopia can compete with commercial preparations in terms of potency and efficacy. Recent work suggests that a Cyclopia extract displays three desirable estrogenic attributes, antagonism of ERα, agonist behaviour through ERβ, and attenuation of oestrogen induced breast cancer proliferation. We have now embarked on characterizing the molecular mechanism of action of Cyclopia by focusing on breast cancer and SHGB, the high affinity carrier of sex steroids in plasma that determines the biological availability of steroids and phytoestrogens.
Interplay of pro-inflammatory cytokines and GR-ligands in the liver
Although the repression of inflammatory cytokines by glucocorticoids is well studied as being the basis of the anti-inflammatory action of glucocorticoids the effect of inflammatory cytokines on glucocorticoid action, especially in the periphery, is less well studied. Having shown in vivo that IL-6 antagonizes the effect of glucocorticoids in the liver we expanded the study in tissue culture and found that glucocorticoids and pro-inflammatory cytokines generally have divergent effects on the GR levels and metabolic enzymes, while their functions are convergent on the acute phase proteins. Further work on the interaction between the stress and inflammatory system is focussing on corticosteroid binding globulin (CBG), which is both a negative acute phase protein synthesised in the liver and the plasma binding protein involved in the transport of glucocorticoids.