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.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Auger AP, Moffatt CA, Blaustein JD (1997) Progesterone-independent activation of rat brain progestin receptors by reproductive stimuli. Endocrinology 138(1):511–514
Behan M, Thomas CF (2005) Sex hormone receptors are expressed in identified respiratory motoneurons in male and female rats. Neuroscience 130(3):725–734
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):193–202
Finer NN et al (2006) Summary proceedings from the apnea-of-prematurity group. Pediatrics 117(3 Pt 2):S47–S51
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):951–962
Galeeva A et al (2010) Postnatal ontogeny of the glucocorticoid receptor in the hippocampus. Vitam Horm 82:367–389
Gulemetova R, Kinkead R (2011) Neonatal stress increases respiratory instability in rat pups. Respir Physiol Neurobiol 176(3):103–109
Haywood SA et al (1999) Fluctuating estrogen and progesterone receptor expression in brainstem norepinephrine neurons through the rat estrous cycle. Endocrinology 140(7):3255–3263
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 1073–1074:71–82
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–R1366
Kinkead R et al (2009) Neonatal maternal separation disrupts regulation of sleep and breathing in adult male rats. Sleep 32(12):1611–1620
Lefter R, Morency CE, Joseph V (2007) Progesterone increases hypoxic ventilatory response and reduces apneas in newborn rats. Respir Physiol Neurobiol 156:9–16
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):312–318
Lonstein JS, Quadros PS, Wagner CK (2001) Effects of neonatal RU486 on adult sexual, parental, and fearful behaviors in rats. Behav Neurosci 115(1):58–70
Mortola JP, Saiki C (1996) Ventilatory response to hypoxia in rats: gender differences. Respir Physiol 106:21–34
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):323–332
Schreiber JR, Hsueh AJ, Baulieu EE (1983) Binding of the anti-progestin RU-486 to rat ovary steroid receptors. Contraception 28(1):77–85
Shahar E et al (2003) Hormone replacement therapy and sleep-disordered breathing. Am J Respir Crit Care Med 167(9):1186–1192
Soliz J, Joseph V (2005) Perinatal steroid exposure and respiratory control during early postnatal life. Respir Physiol Neurobiol 149(1–3):111–122
Zwain IH, Yen SS (1999) Neurosteroidogenesis in astrocytes, oligodendrocytes, and neurons of cerebral cortex of rat brain. Endocrinology 140(8):3843–3852
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media Dordrecht
About this paper
Cite this paper
Fournier, S., Doan, V.D., Joseph, V. (2012). Sex-Specific Effects of Daily Gavage with a Mixed Progesterone and Glucocorticoid Receptor Antagonist on Hypoxic Ventilatory Response in Newborn Rats. In: Nurse, C., Gonzalez, C., Peers, C., Prabhakar, N. (eds) Arterial Chemoreception. Advances in Experimental Medicine and Biology, vol 758. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4584-1_4
Download citation
DOI: https://doi.org/10.1007/978-94-007-4584-1_4
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-4583-4
Online ISBN: 978-94-007-4584-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)