Progesterone stimulates respiration through a central nervous system steroid receptor-mediated mechanism in cat.

Abstract

We have examined the effect on respiration of the steroid hormone progesterone, administered either intravenously or directly into the medulla oblongata in anesthetized and paralyzed male and female cats. The carotid sinus and vagus nerves were cut, and end-tidal Pco2 and temperature were kept constant with servo-controllers. Phrenic nerve activity was used to quantitate central respiratory activity.Repeated doses of progesterone (from 0.1 to 2.0 ,ug/kg, cumulative) caused a sustained (>45 min) facilitation of phrenic nerve activity in female and male cats; however, the response was much more variable in females. Progesterone injected into the region of nucleus tractus solitarii, a respiratory-related area in the medulla oblongata, also caused a prolonged stimulation of respiration. Progesterone administration at high concentration by both routes also caused a substantial hypotension. Identical i.v. doses of other classes of steroid hormones (17f8-estradiol, testosterone, and cortisol) did not elicit the same respiratory effect. Pretreatment with RU 486, a progesterone-receptor antagonist, blocked the facilitatory effect of progesterone. We conclude that progesterone acts centrally through a steroid receptor-mediated mechanism to facilitate respiration.It has been known since the turn of the century that women hyperventilate during pregnancy (1, 2) and during the luteal phase of the menstrual cycle (3). Because the level of circulating progesterone correlates positively with increased ventilation, progesterone has been proposed as the ventilatory stimulant in these conditions (4)-a contention further supported by studies in which exogenously administered progesterone caused hyperventilation in normal male subjects (5, 6) and in patients with breathing disorders (7-12).Even though many animal species hyperventilate during pregnancy when endogenous progesterone levels are elevated (13-15), most fail to respond in a like manner to exogenously administered progesterone under experimental conditions (5,(15)(16)(17). Such data has been interpreted to mean that progesterone is not the respiratory stimulant during pregnancy and the luteal phase of the menstrual cycle. However, a reasonable explanation exists for this apparent discrepancy. Estrogen levels increase during pregnancy, and estrogen causes induction, or upregulation, of progesterone receptors within certain regions of the brain (18,19 Respiratory feedback from the arterial chemoreceptors and the pulmonary mechanoreceptors was blocked by cutting the carotid sinus and vagus nerves. A dorsal laminectomy was performed in one cat, and the spinal cord was transected at C7/T1 to eliminate input from visceral or somatic receptors. One phrenic nerve root (C5) was exposed, cut distally, desheathed, and placed in a bipolar platinum recording electrode that was built into a small acrylic platform placed in a tissue well adjacent to the nerve. Because the electrode had no fixed external attachments (the electrical wires were flexible and moved freely), it was poss...

Effects of human pregnancy on the ventilatory chemoreflex response to carbon dioxide

“…Furthermore, [progesterone] was found to be a significant predictor of changes in the VRTCO 2 within the pooled data. In addition, the relationship between the VRTCO 2 and [progesterone]-to-[estradiol] ratio within the pooled data supports the hypothesis that progesterone receptor availability is an important determinant of pregnancy and gestational hormone-induced changes in ventilatory control (1)(2)(3)6). These data suggest that the effects of gestational hormones on the chemical control of breathing during human pregnancy may be expressed, at least in part, through their influence on the central chemoreflex VRTCO 2 .…”

“…Pregnancy-induced changes in central chemoreflex sensitivity have been attributed to an estrogen-dependent progesterone receptor-mediated central neural mechanism (1)(2)(3)(4)6). However, no significant relationships were observed between central chemoreflex sensitivity with [progesterone] and the [progesterone]-to-[estradiol] ratio within either group.…”

Life-long consequences of postnatal normoxia exposure in rats raised at high altitude

“…These effects are mainly related to ovarian steroids. On one hand, progesterone acts as a respiratory stimulant through peripheral chemoreceptors (22,48) and central respiratory system (4), and, on the other hand, estradiol reduces hypoxic-induced erythropoietin synthesis (36) and pulmonary hypertension (24,49,55). Importantly, however, hematological acclimatization to hypoxia in female rats is also modified by postnatal hypoxia, as observed in our laboratory's previous study at sea level (31).…”

Effect of progesterone-carbachol derivative on perfusion pressure and coronary resistance in isolated rat heart: via activation of the M₂ muscarinic receptor

“…These data suggest that progesterone-carbachol derivative exerts effect on vascular tone. To characterize the molecular mechanism of this phenomenon we analyzed the reports of some investigations which indicate that progesterone induces its effect on blood pressure via activation of the progesterone receptor 22,23 . For this reason, we used mifepristone, a progesterone receptor blocker 14 to determine if the effects of progesterone-carbachol derivative on perfusion pressure were via the progesterone receptor.…”