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Pflügers Archiv - European Journal of Physiology

, Volume 469, Issue 10, pp 1277–1286 | Cite as

Influence of estrous cycle hormonal fluctuations and gonadal hormones on the ventilatory response to hypoxia in female rats

  • Danuzia A. Marques
  • Débora de Carvalho
  • Glauber S. F. da Silva
  • Raphael E. Szawka
  • Janete A. Anselmo-Franci
  • Kênia C. Bícego
  • Luciane H. Gargaglioni
Integrative Physiology
Part of the following topical collections:
  1. Integrative Physiology

Abstract

Sex hormones may influence many physiological processes. Recently, we demonstrated that hormonal fluctuations of cycling female rats do not affect respiratory parameters during hypercapnia. However, it is still unclear whether sex hormones and hormonal fluctuations that occur during the estrous cycle can affect breathing during a hypoxic challenge. Our study aimed to evaluate respiratory, metabolic, and thermal responses to hypoxia in female rats on different days of the estrous cycle (proestrus, estrus, metestrus, and diestrus) and in ovariectomized rats that received replacement with oil (OVX), estradiol (OVX + E2), or a combination of estradiol and progesterone (OVX + E2P). Ventilation (V E), tidal volume (V T), respiratory frequency (fR), oxygen consumption (VO2), and V E/VO2 were not different during the estrous cycle in normoxia or hypoxia. Body temperature (Tb) was higher during estrus, but decreased similarly in all groups during hypoxia. Compared with intact females in estrus, gonadectomized rats also had lower Tb in normoxia, but not in hypoxia. OVX rats experienced a significant drop in the ventilatory response to hypoxia, but hormonal replacement did not restore values to the levels of an intact animal. Our data demonstrate that the different phases of the estrous cycle do not alter ventilation during normoxia and hypoxia, but OVX animals display lower ventilatory responses to hypoxia compared with ovary-intact rats. Because estradiol and progesterone replacement did not cause significant differences in ventilation, our findings suggest that a yet-to-be-defined non-steroidal ovarian hormone is likely to stimulate the ventilatory responses to hypoxia in females.

Keywords

Estrous cycle Sex hormones Breathing Body temperature Castration Hormone replacement 

Notes

Acknowledgements

We thank Euclides Roberto Secato and Ruither O. G. Carolino for excellent technical assistance. This work was supported by the Sao Paulo Research Foundation (FAPESP; 2012/19966-0) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq - 442560/2014-1), INCT-Fisiologia Comparada. G.S.F.S. is supported by a Young Investigator Award (FAPESP; 2013/17606-9 and 2014/12190-1). D.A.M. was the recipient of a FAPESP scholarship 2016/04276-9 and CNPq 140715/2015-0.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Almeida MC, Steiner AA, Coimbra NC, Branco LGS (2004) Thermoeffector neuronal pathways in fever: a study in rats showing a new role of the locus coeruleus. J Physiol 558:283–294. doi: 10.1113/jphysiol.2004.066654 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Bartlett D, Tenney SM (1970) Control of breathing in experimental anemia. Respir Physiol 10:384–395CrossRefPubMedGoogle Scholar
  3. 3.
    Behan M, Kinkead R (2011) Neuronal control of breathing: sex and stress hormones. Compr Physiol 1:2101–2139. doi: 10.1002/cphy.c100027 PubMedGoogle Scholar
  4. 4.
    Behan M, Zabka AG, Thomas CF, Mitchell GS (2003) Sex steroid hormones and the neural control of breathing. Respir Physiol Neurobiol 136:249–263. doi: 10.1016/S1569-9048(03)00086-7 CrossRefPubMedGoogle Scholar
  5. 5.
    Berendsen HHG, Kloosterboer HJ (2003) Oestradiol and mirtazapine restore the disturbed tail-temperature of oestrogen-deficient rats. Eur J Pharmacol. doi: 10.1016/j.ejphar.2003.09.061
  6. 6.
    Biancardi V, Bícego KC, Almeida MC, Gargaglioni LH (2008) Locus coeruleus noradrenergic neurons and CO2 drive to breathing. Pflügers Arch Eur J Physiol 455:1119–1128. doi: 10.1007/s00424-007-0338-8 CrossRefGoogle Scholar
  7. 7.
    Birzniece V, Bäckström T, Johansson I-M, Lindblad C, Lundgren P, Löfgren M, Olsson T, Ragagnin G, Taube M, Turkmen S, Wahlström G, Wang M-D, Wihlbäck A-C, Zhu D (2006) Neuroactive steroid effects on cognitive functions with a focus on the serotonin and GABA systems. Brain Res Rev 51:212–239. doi: 10.1016/j.brainresrev.2005.11.001 CrossRefPubMedGoogle Scholar
  8. 8.
    Block AJ, Boysen PG, Wynne JW, Hunt LA (1979) Sleep apnea, hypopnea and oxygen desaturation in normal subjects. A strong male predominance. N Engl J Med 300:513–517. doi: 10.1056/NEJM197903083001001 CrossRefPubMedGoogle Scholar
  9. 9.
    Boukari R, Rossignol O, Marcouiller F, Bairam A, Joseph V (2016) Membrane Progestrone receptors α and β contribute to regulation of breathing in adult male and female mice. A80-B VIEWING OSA Pathog Color INSTEAD BLACK WHITE Am Thorac Soc A2558–A2558Google Scholar
  10. 10.
    Brinton RD, Thompson RF, Foy MR, Baudry M, Wang J, Finch CE, Morgan TE, Pike CJ, Mack WJ, Stanczyk FZ, Nilsen J (2008) Progesterone receptors: form and function in brain. Front Neuroendocrinol 29:313–339. doi: 10.1016/j.yfrne.2008.02.001 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    de Carvalho D, Bícego KC, de Castro OW, da Silva GSF, Garcia-Cairasco N, Gargaglioni LH (2010) Role of neurokinin-1 expressing neurons in the locus coeruleus on ventilatory and cardiovascular responses to hypercapnia. Respir Physiol Neurobiol 172:24–31. doi: 10.1016/j.resp.2010.04.016 CrossRefPubMedGoogle Scholar
  12. 12.
    Dempsey JA, Olson EB, Skatrud JB (2011) Hormones and neurochemicals in the regulation of breathing. Compr Physiol. doi: 10.1002/cphy.cp030207
  13. 13.
    Dombovy ML, Bonekat HW, Williams TJ, Staats BA (1987) Exercise performance and ventilatory response in the menstrual cycle. Med Sci Sports Exerc 19:111–117CrossRefPubMedGoogle Scholar
  14. 14.
    Dutton K, Blanksby BA, Morton AR (1989) CO2 sensitivity changes during the menstrual cycle. J Appl Physiol 67:517–522PubMedGoogle Scholar
  15. 15.
    Edwards N, Wilcox I, Polo OJ, Sullivan CE (1996) Hypercapnic blood pressure response is greater during the luteal phase of the menstrual cycle. J Appl Physiol 81:2142–2146Google Scholar
  16. 16.
    England SJ, Farhi LE (1976) Fluctuations in alveolar CO2 and in base excess during the menstrual cycle1. Respir Physiol 26:157–161. doi: 10.1016/0034-5687(76)90093-1 CrossRefPubMedGoogle Scholar
  17. 17.
    Fournier S, Gulemetova R, Baldy C, Joseph V, Kinkead R (2015) Neonatal stress affects the aging trajectory of female rats on the endocrine, temperature, and ventilatory responses to hypoxia. Am J Physiol Regul Integr Comp Physiol 308:R659–R667. doi: 10.1152/ajpregu.00418.2014 CrossRefPubMedGoogle Scholar
  18. 18.
    Goldman JM, Murr AS, Cooper RL (2007) The rodent estrous cycle: characterization of vaginal cytology and its utility in toxicological studies. Birth Defects Res B Dev Reprod Toxicol 80:84–97. doi: 10.1002/bdrb.20106 CrossRefPubMedGoogle Scholar
  19. 19.
    Hannhart B, Pickett CK, Moore LG (1990) Effects of estrogen and progesterone on carotid body neural output responsiveness to hypoxia. J Appl Physiol 68:1909–1916PubMedGoogle Scholar
  20. 20.
    Haywood SA, Simonian SX, Van der Beek EM, Bicknell RJ, Herbison AE (1999) Fluctuating estrogen and progesterone receptor expression in brainstem norepinephrine neurons through the rat estrous cycle. Endocrinology 140:3255–3263. doi: 10.1210/endo.140.7.6869 CrossRefPubMedGoogle Scholar
  21. 21.
    Helena C, Gustafsson J-A, Korach K, Pfaff D, Anselmo-Franci JA, Ogawa S (2009) Effects of estrogen receptor alpha and beta gene deletion on estrogenic induction of progesterone receptors in the locus coeruleus in female mice. Endocrine 36:169–177. doi: 10.1007/s12020-009-9207-x CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Hodges MR, Forster HV, Papanek PE, Dwinell MR, Hogan GE (2002) Ventilatory phenotypes among four strains of adult rats. J Appl Physiol 93:974–983CrossRefPubMedGoogle Scholar
  23. 23.
    Joseph V, Doan VD, Morency CE, Lajeunesse Y, Bairam A (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. doi: 10.1016/j.brainres.2005.12.075 CrossRefPubMedGoogle Scholar
  24. 24.
    Joseph V, Niane LM, Bairam A (2012) Antagonism of progesterone receptor suppresses carotid body responses to hypoxia and nicotine in rat pups. Neuroscience 207:103–109. doi: 10.1016/j.neuroscience.2012.01.041 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Joseph V, Soliz J, Soria R, Pequignot J, Favier R, Spielvogel H, Pequignot JM (2002) Dopaminergic metabolism in carotid bodies and high-altitude acclimatization in female rats. Am J Physiol Regul Integr Comp Physiol 282:R765–R773. doi: 10.1152/ajpregu.00398.2001 CrossRefPubMedGoogle Scholar
  26. 26.
    Kent S, Hurd M, Satinoff E (1991) Interactions between body temperature and wheel running over the estrous cycle in rats. Physiol Behav 49:1079–1084CrossRefPubMedGoogle Scholar
  27. 27.
    Knight PG, Glister C (2001) Potential local regulatory functions of inhibins, activins and follistatin in the ovary. Reproduction 121:503–512. doi: 10.1530/reprod/121.4.503 CrossRefPubMedGoogle Scholar
  28. 28.
    Lasota A, Danowska-Klonowska D (2004) Experimental osteoporosis—different methods of ovariectomy in female white rats. Rocz Akad Med Białymst 49(Suppl 1):129–131PubMedGoogle Scholar
  29. 29.
    Macnutt MJ, De Souza MJ, Tomczak SE, Homer JL, Sheel AW (2012) Resting and exercise ventilatory chemosensitivity across the menstrual cycle. J Appl Physiol 112:737–747Google Scholar
  30. 30.
    Marques DA, de Carvalho D, da Silva GSF, Szawka RE, Anselmo-Franci JA, Bícego KC, Gargaglioni LH (2015) Ventilatory, metabolic, and thermal responses to hypercapnia in female rats: effects of estrous cycle, ovariectomy, and hormonal replacement. J Appl Physiol 119:61–68CrossRefPubMedGoogle Scholar
  31. 31.
    Muttukrishna S, Ledger W (2001) Front matter. In: Inhibin, Act. Follistatin Hum. Reprod. Physiol. Published by imperial college press and distributed by world scientific publishing co., pp i–viiiGoogle Scholar
  32. 32.
    Nelson HD (2008) Menopause. Lancet 371:760–770. doi: 10.1016/S0140-6736(08)60346-3 CrossRefPubMedGoogle Scholar
  33. 33.
    Österlund MK (2010) Underlying mechanisms mediating the antidepressant effects of estrogens. Biochim Biophys Acta Gen Subj 1800:1136–1144. doi: 10.1016/j.bbagen.2009.11.001 CrossRefGoogle Scholar
  34. 34.
    Pascotto VM, Guerra MT, Franci JAA, de Camargo JLV, Kempinas WG, Franchi CAS (2015) Effects of a mixture of pesticides on the adult female reproductive system of Sprague-Dawley, Wistar, and Lewis rats. J Toxicol Environ Health A 78:602–616. doi: 10.1080/15287394.2015.1010467 CrossRefPubMedGoogle Scholar
  35. 35.
    Refinetti R, Menaker M (1992) The circadian rhythm of body temperature. Physiol Behav 51:613–637CrossRefPubMedGoogle Scholar
  36. 36.
    Saaresranta T, Polo O (2002) Hormones and breathing. Chest 122:2165–2182. doi: 10.1378/chest.122.6.2165 CrossRefPubMedGoogle Scholar
  37. 37.
    Schlenker EH, Hansen SN (2006) Sex-specific densities of estrogen receptors alpha and beta in the subnuclei of the nucleus tractus solitarius, hypoglossal nucleus and dorsal vagal motor nucleus weanling rats. Brain Res 1123:89–100. doi: 10.1016/j.brainres.2006.09.035 CrossRefPubMedGoogle Scholar
  38. 38.
    Schoene RB, Robertson HT, Pierson DJ, Peterson AP (1981) Respiratory drives and exercise in menstrual cycles of athletic and nonathletic women. J Appl Physiol 50:1300–1305PubMedGoogle Scholar
  39. 39.
    Shahar E, Redline S, Young T, Boland LL, Baldwin CM, Nieto FJ, O’Connor GT, Rapoport DM, Robbins JA (2003) Hormone replacement therapy and sleep-disordered breathing. Am J Respir Crit Care Med 167:1186–1192. doi: 10.1164/rccm.200210-1238OC CrossRefPubMedGoogle Scholar
  40. 40.
    Singletary SJ, Kirsch AJ, Watson J, Karim BO, Huso DL, Hurn PD, Murphy SJ (2005) Lack of correlation of vaginal impedance measurements with hormone levels in the rat. Contemp Top Lab Anim Sci 44:37–42PubMedPubMedCentralGoogle Scholar
  41. 41.
    Slatkovska L, Jensen D, Davies GAL, Wolfe LA (2006) Phasic menstrual cycle effects on the control of breathing in healthy women. Respir Physiol Neurobiol 154:379–388. doi: 10.1016/j.resp.2006.01.011 CrossRefPubMedGoogle Scholar
  42. 42.
    Smith MS, Freeman ME, Neill JD (1975) The control of progesterone secretion during the estrous cycle and early pseudopregnancy in the rat: prolactin, gonadotropin and steroid levels associated with rescue of the corpus luteum of pseudopregnancy. Endocrinology 96:219–226. doi: 10.1210/endo-96-1-219 CrossRefPubMedGoogle Scholar
  43. 43.
    Szawka RE, Rodovalho GV, Monteiro PM, Carrer HF, Anselmo-Franci JA (2009) Ovarian-steroid modulation of locus coeruleus activity in female rats: involvement in luteinising hormone regulation. J Neuroendocrinol 21:629–639. doi: 10.1111/j.1365-2826.2009.01880.x CrossRefPubMedGoogle Scholar
  44. 44.
    Takano N (1985) Ventilatory responses to hypercapnia and hypoxia: the sexual difference and changes during the menstrual cycle. Kokyu To Junkan 33:17–23PubMedGoogle Scholar
  45. 45.
    Tatsumi K, Hannhart B, Moore LG (1995) Influences of sex steroids on ventilation and ventilatory control. Lung Biol Health Dis 79:829–864Google Scholar
  46. 46.
    Tatsumi K, Hannhart B, Pickett CK, Weil JV, Moore LG (1991) Influences of gender and sex hormones on hypoxic ventilatory response in cats. J Appl Physiol 71:1746–1751PubMedGoogle Scholar
  47. 47.
    Tatsumi K, Pickett CK, Jacoby CR, Weil JV, Moore LG (1997) Role of endogenous female hormones in hypoxic chemosensitivity. J Appl Physiol 83:1706–1710PubMedGoogle Scholar
  48. 48.
    Uchida Y, Kano M, Yasuhara S, Kobayashi A, Tokizawa K, Nagashima K (2010) Estrogen modulates central and peripheral responses to cold in female rats. J Physiol Sci 60:151–160. doi: 10.1007/s12576-009-0079-x CrossRefPubMedGoogle Scholar
  49. 49.
    Uchida Y, Tokizawa K, Nakamura M, Mori H, Nagashima K (2010) Estrogen in the medial preoptic nucleus of the hypothalamus modulates cold responses in female rats. Brain Res 1339:49–59. doi: 10.1016/j.brainres.2010.04.021 CrossRefPubMedGoogle Scholar
  50. 50.
    Uppari NP, Joseph V, Bairam A (2017) Respiratory responses to progesterone and allopregnanolone following chronic caffeine treatment in newborn female rats. Respir Physiol Neurobiol 240:32–40. doi: 10.1016/j.resp.2017.01.017 CrossRefPubMedGoogle Scholar
  51. 51.
    Vigier B, Picard JY, Tran D, Legeai L, Josso N (1984) Production of anti-Müllerian hormone: another homology between Sertoli and granulosa cells. Endocrinology 114:1315–1320. doi: 10.1210/endo-114-4-1315 CrossRefPubMedGoogle Scholar
  52. 52.
    Wenninger JM, Olson EB, Cotter CJ, Thomas CF, Behan M (2009) Hypoxic and hypercapnic ventilatory responses in aging male vs. aging female rats. J Appl Physiol 106:1522–1528. doi: 10.1152/japplphysiol.90802.2008 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    White DP, Douglas NJ, Pickett CK, Zwillich CW, Weil JV (1983) Sleep deprivation and the control of ventilation. Am Rev Respir Dis 128:984–986. doi: 10.1164/arrd.1983.128.6.984 PubMedGoogle Scholar
  54. 54.
    Yanase M, Tanaka H, Nakayama T (1989) Effects of estrus cycle on thermoregulatory responses during exercise in rats. Eur J Appl Physiol Occup Physiol 58:446–451CrossRefPubMedGoogle Scholar
  55. 55.
    Young T, Peppard PE, Gottlieb DJ (2002) Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med 165:1217–1239. doi: 10.1164/rccm.2109080 CrossRefPubMedGoogle Scholar
  56. 56.
    Zabka A, Behan M, Mitchell G (2001) Selected contribution: time-dependent hypoxic respiratory responses in female rats are influenced by age and by the estrus cycle. J Appl Physiol 91:2831–2838. doi: 10.1016/0034-5687(96)00017-5

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Danuzia A. Marques
    • 1
  • Débora de Carvalho
    • 2
  • Glauber S. F. da Silva
    • 1
  • Raphael E. Szawka
    • 3
  • Janete A. Anselmo-Franci
    • 4
  • Kênia C. Bícego
    • 1
  • Luciane H. Gargaglioni
    • 1
  1. 1.Department of Animal Morphology and PhysiologySão Paulo State University, UNESP FCAV at JaboticabalSão PauloBrazil
  2. 2.Federal Institute of ParaParaBrazil
  3. 3.Department of Physiology and Biophysics, Institute of Biological SciencesFederal University of Minas GeraisMinas GeraisBrazil
  4. 4.Department of Morphology, Stomatology and Physiology, Dental School of Ribeirao PretoUniversity of São PauloSão PauloBrazil

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