Progesterone reverses the neuronal responses to hypoxia in rat nucleus tractus solitarius in vitro.
The nucleus tractus solitarius (NTS) is a relay nucleus that integrates peripheral chemoreceptor input in response to hypoxia and hence influences the generation of respiratory rhythm. Several studies have shown that administration of progesterone stimulates ventilatory responses to hypoxia. There is some evidence that this steroid hormone can act at the level of the arterial peripheral chemoreceptors, whereas its action in the central nervous system remains unclear. To investigate a possible central involvement during hypoxia, we studied the effect of progesterone on neuronal activities recorded extra- and intracellularly in the NTS using brainstem slices. Central chemosensitivity was tested by comparing synaptic activity and intrinsic electro-responsiveness of 38 neurones during normoxia and hypoxia. In more than two-thirds of neurones recorded, hypoxia elicited a hyperpolarisation, a decrease in the input resistance and a decrease in spontaneous activity. In the remaining neurones (n = 12) hypoxia elicited a depolarisation and an increase in spontaneous activity. In all neurones tested, synaptic potentials evoked by stimulation of the tractus solitarius were decreased by hypoxia. While progesterone (1 microM) had no effect under normoxic conditions, it partially reversed all hypoxic neuronal responses. This effect developed over 2-3 min and reversed within 5 min suggesting a non-genomic mechanism of action. Taken together these results suggest that progesterone interacts with the hypoxia-induced cellular signalling. We conclude that in the NTS, transmission of afferent signals is reduced by hypoxia and restored by progesterone administration. Such a mechanism may contribute to the stimulation of breathing in response to hypoxia observed following progesterone administration in vivo.
Pascual
Olivier
O
UPR 2216 Neurobiologie Génétique et Intégrative CNRS, Institut de Neurobiologie Alfred Fessard, 1 Avenue de la Terrasse, 91198 Gif/Yvette, France. opascual@iaf.cnrs-gif.fr
Morin-Surun
Marie-Pierre
MP
Barna
Barbara
B
Denavit-Saubié
Monique
M
Pequignot
Jean-Marc
JM
Champagnat
Jean
J
D000818:Animals; D017097:Electric Impedance; D004558:Electric Stimulation; D004594:Electrophysiology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000187:drug effects* / Q000503:physiopathology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects
D011374:Progesterone