Modulation of mineralocorticoid receptor mRNA levels in human monocytic cells (U 937) by hypericum perforatum

The mineralocorticoid receptor (MR) has been implicated to participate in the neuroendocrine disturbances in major depression (MD). Therefore, this receptor system should also be affected by antidepressive treatment. Up to now, only few data have revealed such actions of antidepressants. In order to study the effects of hypericum perforatum on MR functions, we examined its effects on MR gene-expression in human monocytic blood cells as a peripheral model for neuroendocrine effects of hypericum in MD. Under our conditions, treatment of blood cells with an extract of hypericum perforatum (LI 160) affected cellular mRNA levels of the MR at concentrations similar to antidepressive treatment in the human in a dose-dependent and biphasic manner. Between the concentrations of 0.625µg/ml and 2.5µg/ml, a significant down-regulation was detected, whereas a reciprocal effect was observed between concentrations of 2.5µg/ml and 10µg/ml, which significantly up-regulated the MR mRNA-levels. Our data show, that hypericum affects MR-mRNA levels in our model system. Such an influence on MR-mediated cellular signal transduction has previously been suggested as an important way of action for a number at antidepressants. Thus, it could be hypothesized that hypericum also affects the depressive psychopathology by acting at neuroendocrine dysfunctions in MD via the MR-receptor system.