Advertisement

Sex-Specific Effects of Daily Gavage with a Mixed Progesterone and Glucocorticoid Receptor Antagonist on Hypoxic Ventilatory Response in Newborn Rats

  • Stéphanie Fournier
  • Van Diep Doan
  • Vincent JosephEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 758)

Abstract

We tested the hypothesis that daily gavage with mifepristone, a mixed progesterone/glucocorticoid receptor antagonist would alter hypoxic ventilatory response (HVR) in newborn male and female rats. Rats were treated with mifepristone (40µg/g/day), or vehicle between postnatal days 3–12, and used at 10–12 days of age to record baseline ventilatory and metabolic values using whole body plethysmography. HVR was tested by exposing the animals to 14% and 12% O2 for 20 minutes each. HVR was enhanced by mifepristone treatment, mainly due to an effect on tidal volume that remained higher in mifepristone treated rats during both levels of hypoxic exposure. This effect was sex-specific being apparent only in male rats. In Vehicle treated rats, HVR was higher in females than in males, which was also due to a higher tidal volume in hypoxia (at 14 and 12% O2). We conclude that the activity of the progesterone and/or glucocorticoid receptors modulates respiratory control in rat pups, and that these effects are different in males and females.

Keywords

Newborn rats Gavage Mifepristone Steroid receptor antagonist Progesterone Glucocorticoid Hypoxic ventilatory response Whole body plethysmography 

References

  1. Auger AP, Moffatt CA, Blaustein JD (1997) Progesterone-independent activation of rat brain progestin receptors by reproductive stimuli. Endocrinology 138(1):511–514PubMedCrossRefGoogle Scholar
  2. Behan M, Thomas CF (2005) Sex hormone receptors are expressed in identified respiratory motoneurons in male and female rats. Neuroscience 130(3):725–734PubMedCrossRefGoogle Scholar
  3. Cole TJ et al (2001) GRKO mice express an aberrant dexamethasone-binding glucocorticoid receptor, but are profoundly glucocorticoid resistant. Mol Cell Endocrinol 173(1–2):193–202PubMedCrossRefGoogle Scholar
  4. Finer NN et al (2006) Summary proceedings from the apnea-of-prematurity group. Pediatrics 117(3 Pt 2):S47–S51PubMedGoogle Scholar
  5. Fournier S et al (2007) Chronic corticosterone elevation and sex-specific augmentation of the hypoxic ventilatory response in awake rats. J Physiol 584(Pt 3):951–962PubMedCrossRefGoogle Scholar
  6. Galeeva A et al (2010) Postnatal ontogeny of the glucocorticoid receptor in the hippocampus. Vitam Horm 82:367–389PubMedCrossRefGoogle Scholar
  7. Gulemetova R, Kinkead R (2011) Neonatal stress increases respiratory instability in rat pups. Respir Physiol Neurobiol 176(3):103–109PubMedCrossRefGoogle Scholar
  8. Haywood SA et al (1999) Fluctuating estrogen and progesterone receptor expression in brainstem norepinephrine neurons through the rat estrous cycle. Endocrinology 140(7):3255–3263PubMedCrossRefGoogle Scholar
  9. Joseph V et al (2006) Expression of sex-steroid receptors and steroidogenic enzymes in the carotid body of adult and newborn male rats. Brain Res 1073–1074:71–82PubMedCrossRefGoogle Scholar
  10. Julien C, Bairam A, Joseph V (2008) Chronic intermittent hypoxia reduces ventilatory long-term facilitation and enhances apnea frequency in newborn rats. Am J Physiol Regul Integr Comp Physiol 294(4):R1356–R1366PubMedCrossRefGoogle Scholar
  11. Kinkead R et al (2009) Neonatal maternal separation disrupts regulation of sleep and breathing in adult male rats. Sleep 32(12):1611–1620PubMedGoogle Scholar
  12. Lefter R, Morency CE, Joseph V (2007) Progesterone increases hypoxic ventilatory response and reduces apneas in newborn rats. Respir Physiol Neurobiol 156:9–16PubMedCrossRefGoogle Scholar
  13. Lefter R, Doan VD, Joseph V (2008) Contrasting effects of estradiol and progesterone on respiratory pattern and hypoxic ventilatory response in newborn male rats. Respir Physiol Neurobiol 164(3):312–318PubMedCrossRefGoogle Scholar
  14. Lonstein JS, Quadros PS, Wagner CK (2001) Effects of neonatal RU486 on adult sexual, parental, and fearful behaviors in rats. Behav Neurosci 115(1):58–70PubMedCrossRefGoogle Scholar
  15. Mortola JP, Saiki C (1996) Ventilatory response to hypoxia in rats: gender differences. Respir Physiol 106:21–34PubMedCrossRefGoogle Scholar
  16. Niane L, Joseph V, Bairam A (2009) Role of cholinergic-nicotinic receptors on hypoxic chemoreflex during postnatal development in rats. Respir Physiol Neurobiol 169(3):323–332PubMedCrossRefGoogle Scholar
  17. Schreiber JR, Hsueh AJ, Baulieu EE (1983) Binding of the anti-progestin RU-486 to rat ovary steroid receptors. Contraception 28(1):77–85PubMedCrossRefGoogle Scholar
  18. Shahar E et al (2003) Hormone replacement therapy and sleep-disordered breathing. Am J Respir Crit Care Med 167(9):1186–1192PubMedCrossRefGoogle Scholar
  19. Soliz J, Joseph V (2005) Perinatal steroid exposure and respiratory control during early postnatal life. Respir Physiol Neurobiol 149(1–3):111–122PubMedCrossRefGoogle Scholar
  20. Zwain IH, Yen SS (1999) Neurosteroidogenesis in astrocytes, oligodendrocytes, and neurons of cerebral cortex of rat brain. Endocrinology 140(8):3843–3852PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Stéphanie Fournier
    • 1
  • Van Diep Doan
    • 1
  • Vincent Joseph
    • 1
    Email author
  1. 1.Department of PediatricsLaval University, Centre de Recherche CHUQ, Hôpital St-François d’AssiseQuebecCanada

Personalised recommendations