Funding outcome

Progesterone (a female sex hormone) has been implicated in the potentiation of breathing during pregnancy and specific phases of the menstrual cycle in women. Additionally, the reduction in circulating progesterone levels in women is proposed to be a main contributing factor to the increased frequency of sleep disordered breathing in menopause, although the mechanisms through which progesterone affects breathing are not yet fully understood. Recent results in our laboratory show that a potent drug that activates progesterone receptor (etonogestrel) potentiates breathing in healthy condition, and recovers breathing impairment in a rodent model in which the response to inhaled CO2 (which usually stimulate breathing) is impaired. In this project we will continue our investigation to determine whether etonogestrel act through the hypothalamus, a brain region that is activated by CO2 and stimulate the respiratory network in the brain and express high levels of progesterone receptors. We will infuse etonogestrel over a 3 week period in the hypothalamus and we will test the respiratory effects in freely behaving female rats. We will perform these experiments in healthy rats and in the rat model that we have recently developed (Janes et al, Acta Physiologica, 2024). We hypothesize that etonogestrel with stimulate breathing in both experimental models and will promote respiratory recovery in the model of impaired response to CO2. Results from our experiments will help identify the effects and mechanisms of action of sex hormones in the brain, and how the stimulation of the hypothalamus influences aspects of respiratory control.