The reciprocal regulation of stress hormones and GABA A receptors

Abstract

Stress-derived steroid hormones regulate the expression and function of GABA A receptors GABA ARs). Changes in GABAaR subunit expression have been demonstrated under conditions of altered steroid hormone levels, such as stress, as well as following exogenous steroid hormone administration. In addition to the effects of stress-derived steroid hormones on GABA AR subunit expression, stress hormones can also be metabolized to neuroactive derivatives which can alter the function of GABA ARs. Neurosteroids allosterically modulate GABA ARs at concentrations comparable to those during stress. In addition to the actions of stress-derived steroid hormones on GABA ARs, GABA ARs reciprocally regulate the production of stress hormones. The stress response is mediated by the hypothalamic-pituitary-adrenal (HPA) axis, the activity of which is governed by corticotropin releasing hormone (CRH) neurons. The activity of CRH neurons is largely controlled by robust GABAergic inhibition. Recently, it has been demonstrated that CRH neurons are regulated by neurosteroid-sensitive, GABA AR δ subunit-containing receptors representing a novel feedback mechanism onto the HPA axis. Further, it has been demonstrated that neurosteroidogenesis and neurosteroid actions on GABA AR δ subunit-containing receptors on CRH neurons are necessary to mount the physiological response to stress. Here we review the literature describing the effects of steroid hormones on GABA ARs as well as the importance of GABA ARs in regulating the production of steroid hormones. This review incorporates what we currently know about changes in GABAaRs following stress and the role in HPA axis regulation. © 2012 Mody and Maguire.