Ovarian steroids act as respiratory stimulant and antioxidant against the causes and consequences of sleep-apnea in women

Evidence supports the importance of ovarian hormones as potential tools against sleep apneas in women. On one hand, progesterone is largely acknowledged as being a respiratory stimulant that reduces the frequency of apneas, but the underlying mechanisms remain poorly understood. Recent studies in mice showed that the respiratory effects of progesterone are mediated by at least two classes of progesterone receptors, including the nuclear (nPR) and membrane receptors (mPR). Some of these receptors (nPR) have sex-specific effects on the frequency of apneas recorded during sleep in mice, while mPR beta acts in males as well as in females. Moreover, sleep apnea is a condition that induces an oxidative stress response in several tissues, and this contributes to the deleterious consequences of sleep apneas, including the development of hypertension. While estradiol is recognized as an antioxidant hormone, its potential protective role has remained mostly ignored in the field. We will review recent data supporting an antioxidant role of estradiol in female rats exposed to intermittent hypoxia, a reliable animal model of sleep apnea. Since estradiol has two main receptors (ER alpha and ER beta) we will discuss their relative implications, and present new data showing a key role for ER alpha to prevent the hypertension induced by intermittent hypoxia. Overall this review highlights the fact that ovarian hormones could potentially be used as efficient tools against the causes (i.e. instabilities of the respiratory control system) and consequences (oxidative stress) of sleep apnea. (C) 2017 Elsevier B.V. All rights reserved.