title: The progestin etonogestrel enhances the respiratory response to metabolic acidosis in newborn rats. Evidence for a mechanism involving supramedullary structures.
abstract: Central congenital hypoventilation syndrome is a neuro-respiratory disease characterized by the dysfunction of the CO2/H(+) chemosensitive neurons of the retrotrapezoid nucleus/parafacial respiratory group. A recovery of CO2/H(+) chemosensitivity has been observed in some central congenital hypoventilation syndrome patients coincidental with contraceptive treatment by a potent progestin, desogestrel (Straus et al., 2010). The mechanisms of this progestin effect remain unknown, although structures of medulla oblongata, midbrain or diencephalon are known to be targets for progesterone. In the present study, on ex vivo preparations of central nervous system of newborn rats, we show that acute exposure to etonogestrel (active metabolite of desogestrel) enhanced the increased respiratory frequency induced by metabolic acidosis via a mechanism involving supramedullary structures located in pontine, mesencephalic or diencephalic regions.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1158, Neurophysiologie Respiratoire Expérimentale et Clinique, F-75005 Paris, France; INSERM, UMR_S 1158, Neurophysiologie Respiratoire Expérimentale et Clinique, F-75005 Paris, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Loiseau
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1158, Neurophysiologie Respiratoire Expérimentale et Clinique, F-75005 Paris, France; INSERM, UMR_S 1158, Neurophysiologie Respiratoire Expérimentale et Clinique, F-75005 Paris, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Osinski
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1158, Neurophysiologie Respiratoire Expérimentale et Clinique, F-75005 Paris, France; INSERM, UMR_S 1158, Neurophysiologie Respiratoire Expérimentale et Clinique, F-75005 Paris, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Joubert
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1158, Neurophysiologie Respiratoire Expérimentale et Clinique, F-75005 Paris, France; INSERM, UMR_S 1158, Neurophysiologie Respiratoire Expérimentale et Clinique, F-75005 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Service d'Explorations Fonctionnelles de la Respiration, de l'Exercice et de la Dyspnée, F-75651 Paris, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Straus
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1158, Neurophysiologie Respiratoire Expérimentale et Clinique, F-75005 Paris, France; INSERM, UMR_S 1158, Neurophysiologie Respiratoire Expérimentale et Clinique, F-75005 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Service de Pneumologie et Réanimation Médicale, F-75651 Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Similowski
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1158, Neurophysiologie Respiratoire Expérimentale et Clinique, F-75005 Paris, France; INSERM, UMR_S 1158, Neurophysiologie Respiratoire Expérimentale et Clinique, F-75005 Paris, France. Electronic address: laurence.bodineau@upmc.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Bodineau
mesh_terms: D000138:Acidosis / Q000503:physiopathology*; D000818:Animals; D000831:Animals, Newborn; D017135:Desogestrel / Q000494:pharmacology*; D004027:Diencephalon / Q000187:drug effects / Q000503:physiopathology; D006863:Hydrogen-Ion Concentration; D008526:Medulla Oblongata / Q000187:drug effects / Q000503:physiopathology; D008636:Mesencephalon / Q000187:drug effects / Q000503:physiopathology; D011372:Progestins / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D012125:Respiratory Center / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D011372:Progestins; C044815:etonogestrel; D017135:Desogestrel
keywords: CO(2)/H(+) chemosensitivity; Central congenital hypoventilation syndrome; Central respiratory drive; Etonogestrel; Ex vivo preparations of central nervous system; Supramedullary structures