Isoflurane stress induces glucocorticoid production in mouse lymphoid organs

in Journal of Endocrinology
Authors:
Jordan E Hamden Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada
Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada

Search for other papers by Jordan E Hamden in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0002-8152-6113
,
Melody Salehzadeh Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada
Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada

Search for other papers by Melody Salehzadeh in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0003-0172-939X
,
Katherine M Gray Department of Psychology, University of British Columbia, Vancouver, British Columbia, Canada
Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

Search for other papers by Katherine M Gray in
Current site
Google Scholar
PubMed
Close
,
Brandon J Forys Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada
Department of Psychology, University of British Columbia, Vancouver, British Columbia, Canada

Search for other papers by Brandon J Forys in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0003-0316-3027
, and
Kiran K Soma Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada
Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada
Department of Psychology, University of British Columbia, Vancouver, British Columbia, Canada
Graduate Program in Neuroscience, University of British Columbia, Vancouver, British Columbia, Canada

Search for other papers by Kiran K Soma in
Current site
Google Scholar
PubMed
Close

Correspondence should be addressed to K K Soma: ksoma@psych.ubc.ca
Restricted access
Rent on DeepDyve

Sign up for journal news

Glucocorticoids (GCs) are secreted by the adrenal glands and locally produced by lymphoid organs. Adrenal GC secretion at baseline and in response to stressors is greatly reduced during the stress hyporesponsive period (SHRP) in neonatal mice (postnatal day (PND) 2–12). It is unknown whether lymphoid GC production increases in response to stressors during the SHRP. Here, we administered an acute stressor (isoflurane anesthesia) to mice before, during, and after the SHRP and measured systemic and local GCs via mass spectrometry. We administered isoflurane, vehicle control (oxygen), or neither (baseline) at PND 1, 5, 9, or 13 and measured progesterone and six GCs in blood, bone marrow, thymus, and spleen. At PND1, blood and lymphoid GC levels were high and did not respond to stress. At PND5, blood GC levels were very low and increased slightly after stress, while lymphoid GC levels were also low but increased greatly after stress. At PND9, blood and lymphoid GC levels were similar at baseline and increased similarly after stress. At PND13, blood GC levels were higher than lymphoid GC levels at baseline, and blood GC levels showed a greater response to stress. These data demonstrate the remarkable plasticity of GC physiology during the postnatal period, show that local steroid levels do not reflect systemic steroid levels, provide insight into the SHRP, and identify a potential mechanism by which early-life stressors can alter immunity in adulthood.

Supplementary Materials

    • Supplemental Figure 1. In post-natal day 5, 9, and 13 mice, difference in tissue – blood deoxycorticosterone (DOC) levels in (A) bone marrow, (B) thymus, (C) spleen. Data are show as mean ± SEM. n=10 for all ages and tissues.
    • Supplemental Figure 2. In post-natal day 5, 9, and 13 mice, difference in tissue – blood deoxycorticosterone (DOC) levels in (A) bone marrow, (B) thymus, (C) spleen. Data are show as mean ± SEM. n=10 for all ages and tissues.
    • Supplemental Figure 3. In post-natal day 5 mice, differences in isoflurane – baseline corticosterone levels in blood, bone marrow, thymus, and spleen. Means are shown. Error bars are not present because different animals were used for each treatment group. To obtain differences between isoflurane and baseline groups, the average of the baseline group was subtracted from the average of the isoflurane group for each tissue.
    • Supplemental Table 1. Summary of p-values from Tukey Post-Hoc tests for Mixed-Effects analysis of steroid levels.
    • Supplemental Table 2: Summary of p-values from Tukey Post-Hoc tests for Two-Way ANOVA of Tissue-Blood corticosterone levels.
    • Supplemental Table 3: Mean and 95% CI for the isoflurane group in Tissue-Blood at PND5, PND9, and PND13.
    • Supplemental Table 4: Multiple linear regression analysis examining the factors that predict local corticosterone levels.

 

  • Collapse
  • Expand
  • Avitsur R & Sheridan JF 2009 Neonatal stress modulates sickness behavior. Brain, Behavior, and Immunity 23 977985. (https://doi.org/10.1016/j.bbi.2009.05.056)

  • Bilbo SD, Biedenkapp JC, Der-Avakian A, Watkins LR, Rudy JW & Maier SF 2005 Neonatal infection-induced memory impairment after lipopolysaccharide in adulthood is prevented via caspase-1 inhibition. Journal of Neuroscience 25 80008009. (https://doi.org/10.1523/JNEUROSCI.1748-05.2005)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Boksa P 1997 Early developmental profiles of plasma corticosterone are altered by birth condition in the rat: a comparison of vaginal birth, cesarean section, and cesarean section with added anoxia. Pediatric Research 41 3443. (https://doi.org/10.1203/00006450-199701000-00006)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bonneville M, O’Brien RL & Born WK 2010 γδ T cell effector functions: a blend of innate programming and acquired plasticity. Nature Reviews: Immunology 10 467478. (https://doi.org/10.1038/nri2781)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Butte JC, Kakihana R & Noble EP 1972 Rat and mouse brain corticosterone. Endocrinology 90 10911100. (https://doi.org/10.1210/endo-90-4-1091)

  • Butte JC, Kakihana R, Farnham ML & Noble EP 1973 The relationship between brain and plasma corticosterone stress response in developing rats. Endocrinology 92 17751779. (https://doi.org/10.1210/endo-92-6-1775)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cain DW, Bortner CD, Diaz-Jimenez D, Petrillo MG, Gruver-Yates A & Cidlowski JA 2020 Murine glucocorticoid receptors orchestrate B cell migration selectively between bone marrow and blood. Journal of Immunology 205 619629. (https://doi.org/10.4049/jimmunol.1901135)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cirulli F, Santucci D, Laviola G, Alleva E & Levine S 1994 Behavioral and hormonal responses to stress in the newborn mouse: effects of maternal deprivation and chlordiazepoxide. Developmental Psychobiology 27 301316. (https://doi.org/10.1002/dev.420270505)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cirulli F, Adriani W & Laviola G 1997 Sexual segregation in infant mice: behavioural and neuroendocrine responses to d-amphetamine administration. Psychopharmacology 134 140152. (https://doi.org/10.1007/s002130050435)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Clarke BL & Bost KL 1989 Differential expression of functional adrenocorticotropic hormone receptors by subpopulations of lymphocytes. Journal of Immunology 143 464469.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cortez D, Stoica G, Pierce JH & Pendergast AM 1996 The BCR-ABL tyrosine kinase inhibits apoptosis by activating a Ras-dependent signaling pathway. Oncogene 13 25892594.(https://doi.org/10.1038/sj.onc.1201400)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cote TE & Yasumura S 1975 Effect of ACTH and histamine stress on serum corticosterone and adrenal cyclic AMP levels in immature rats. Endocrinology 96 10441047. (https://doi.org/10.1210/endo-96-4-1044)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • D’Amato FR, Cabib S, Puglisi-Allegra S, Patacchioli FR, Cigliana G, Maccari S & Angelucci L 1992 Effects of acute and repeated exposure to stress on the hypothalamo-pituitary-adrenocortical activity in mice during postnatal development. Hormones and Behavior 26 474485. (https://doi.org/10.1016/0018-506x(9290015-n)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • del Rey A, Furukawa H, Monge-Arditi G, Kabiersch A, Voigt KH & Besedovsky HO 1996 Alterations in the pituitary–adrenal axis of adult mice following neonatal exposure to interleukin-1. Brain, Behavior, and Immunity 10 235248. (https://doi.org/10.1006/brbi.1996.0021)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Franks AL, Berry KJ & DeFranco DB 2020 Prenatal drug exposure and neurodevelopmental programming of glucocorticoid signalling. Journal of Neuroendocrinology 32 e12786. (https://doi.org/10.1111/jne.12786)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Garvy BA, King LE, Telford WG, Morford LA & Fraker PJ 1993 Chronic elevation of plasma corticosterone causes reductions in the number of cycling cells of the B lineage in murine bone marrow and induces apoptosis. Immunology 80 587592.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gray P 1971 Pituitary-adrenocortical response to stress in the neonatal rat. Endocrinology 89 11261128. (https://doi.org/10.1210/endo-89-4-1126)

  • Gruver-Yates AL, Quinn MA & Cidlowski JA 2014 Analysis of glucocorticoid receptors and their apoptotic response to dexamethasone in male murine B cells during development. Endocrinology 155 463474. (https://doi.org/10.1210/en.2013-1473)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gunnar MR & Donzella B 2002 Social regulation of the cortisol levels in early human development. Psychoneuroendocrinology 27 199220. (https://doi.org/10.1016/s0306-4530(0100045-2)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Haltmeyer GC, Denenberg VH, Thatcher J & Zarrow MX 1966 Response of the adrenal cortex of the neonatal rat after subjection to stress. Nature 212 13711373. (https://doi.org/10.1038/2121371a0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hamden JE, Salehzadeh M, Jalabert C, O’Leary TP, Snyder JS, Gomez-Sanchez CE & Soma KK 2019 Measurement of 11-dehydrocorticosterone in mice, rats and songbirds: effects of age, sex and stress. General and Comparative Endocrinology 281 173182. (https://doi.org/10.1016/j.ygcen.2019.05.018)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hamden JE, Gray KM, Salehzadeh M, Kachkovski GV, Forys BJ, Ma C, Austin SH & Soma KK 2021 Steroid profiling of glucocorticoids in microdissected mouse brain across development. Developmental Neurobiology 81 189206. (https://doi.org/10.1002/dneu.22808)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Henning SJ 1978 Plasma concentrations of total and free corticosterone during development in the rat. American Journal of Physiology 235 E451–E456. (https://doi.org/10.1152/ajpendo.1978.235.5.E451)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hodgson DM, Knott B & Walker FR 2001 Neonatal endotoxin exposure influences HPA responsivity and impairs tumor immunity in Fischer 344 rats in adulthood. Pediatric Research 50 750755. (https://doi.org/10.1203/00006450-200112000-00020)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Iwata M, Hanaoka S & Sato K 1991 Rescue of thymocytes and T cell hybridomas from glucocorticoid-induced apoptosis by stimulation via the T cell receptor/CD3 complex: a possible in vitro model for positive selection of the T cell repertoire. European Journal of Immunology 21 643648. (https://doi.org/10.1002/eji.1830210316)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Johnson EW, Hughes Jr TK & Smith EM 2001 ACTH receptor distribution and modulation among murine mononuclear leukocyte populations. Journal of Biological Regulators and Homeostatic Agents 15 156162.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lu FW, Yasutomo K, Goodman GB, McHeyzer-Williams LJ, McHeyzer-Williams MG, Germain RN & Ashwell JD 2000 Thymocyte resistance to glucocorticoids leads to antigen-specific unresponsiveness due to ‘holes’ in the T cell repertoire. Immunity 12 183192. (https://doi.org/10.1016/s1074-7613(0080171-5)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • McCormick CM, Kehoe P & Kovacs S 1998 Corticosterone release in response to repeated, short episodes of neonatal isolation: evidence of sensitization. International Journal of Developmental Neuroscience 16 175185. (https://doi.org/10.1016/s0736-5748(9800026-4)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Meaney MJ, Sapolsky RM & McEwen BS 1985 The development of the glucocorticoid receptor system in the rat limbic brain: ontogeny and autoregulation. Brain Research 350 159164. (https://doi.org/10.1016/0165-3806(8590259-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Miller AH, Spencer RL, Stein M & McEwen BS 1990 Adrenal steroid receptor binding in spleen and thymus after stress or dexamethasone. American Journal of Physiology 259 E405–E412. (https://doi.org/10.1152/ajpendo.1990.259.3.E405)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mittelstadt PR, Monteiro JP & Ashwell JD 2012 Thymocyte responsiveness to endogenous glucocorticoids is required for immunological fitness. Journal of Clinical Investigation 122 23842394. (https://doi.org/10.1172/JCI63067)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mittelstadt PR, Taves MD & Ashwell JD 2018 Cutting edge: de novo glucocorticoid synthesis by thymic epithelial cells regulates antigen-specific thymocyte selection. Journal of Immunology 200 19881994. (https://doi.org/10.4049/jimmunol.1701328)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nishi M, Horii-Hayashi N & Sasagawa T 2014 Effects of early life adverse experiences on the brain: implications from maternal separation models in rodents. Frontiers in Neuroscience 8 166. (https://doi.org/10.3389/fnins.2014.00166)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Romero LM & Reed JM 2005 Collecting baseline corticosterone samples in the field: is under 3 min good enough? Comparative Biochemistry and Physiology 140 7379. (https://doi.org/10.1016/j.cbpb.2004.11.004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sapolsky RM & Meaney MJ 1986 Maturation of the adrenocortical stress response: neuroendocrine control mechanisms and the stress hyporesponsive period. Brain Research 396 6476. (https://doi.org/10.1016/s0006-8993(8680190-1)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Schmidt MV 2019 Stress-hyporesponsive period. In Stress: Physiology, Biochemistry, and Pathology, pp. 4956. Elsevier.

  • Schmidt KL & Soma KK 2008 Cortisol and corticosterone in the songbird immune and nervous systems: local vs. systemic levels during development. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology 295 R103R110. (https://doi.org/10.1152/ajpregu.00002.2008)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Schmidt MV, Oitzl MS, Levine S & de Kloet ER 2002 The HPA system during the postnatal development of CD1 mice and the effects of maternal deprivation. Brain Research: Developmental Brain Research 139 3949. (https://doi.org/10.1016/s0165-3806(0200519-9)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Schmidt MV, Enthoven L, van der Mark M, Levine S, de Kloet ER & Oitzl MS 2003 The postnatal development of the hypothalamic-pituitary-adrenal axis in the mouse. International Journal of Developmental Neuroscience 21 125132. (https://doi.org/10.1016/s0736-5748(0300030-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Schmidt KL, Pradhan DS, Shah AH, Charlier TD, Chin E & Soma KK 2008 Neurosteroids, immunosteroids, and the Balkanization of endocrinology. General and Comparative Endocrinology 157 266274. (https://doi.org/10.1016/j.ygcen.2008.03.025)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Schoenfeld NM, Leathem JH & Rabii J 1980 Maturation of adrenal stress responsiveness in the rat. Neuroendocrinology 31 101105. (https://doi.org/10.1159/000123058)

  • Shanks N, Windle RJ, Perks PA, Harbuz MS, Jessop DS, Ingram CD & Lightman SL 2000 Early-life exposure to endotoxin alters hypothalamic-pituitary-adrenal function and predisposition to inflammation. PNAS 97 56455650. (https://doi.org/10.1073/pnas.090571897)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Spinedi E, Chisari A, Pralong F & Gaillard RC 1997 Sexual dimorphism in the mouse hypothalamic-pituitary-adrenal axis function after endotoxin and insulin stresses during development. Neuroimmunomodulation 4 7783. (https://doi.org/10.1159/000097324)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Suzuki S & Nakano K 1986 LPS-caused secretion of corticosterone is mediated by histamine through histidine decarboxylase. American Journal of Physiology 250 E243E247. (https://doi.org/10.1152/ajpendo.1986.250.3.E243)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Tang F & Phillips JG 1977 Pituitary-adrenal response to ether stress in the neonatal rat. Journal of Endocrinology 75 183184. (https://doi.org/10.1677/joe.0.0750183)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Taves MD & Ashwell JD 2021 Glucocorticoids in T cell development, differentiation and function. Nature Reviews Immunology 21 233243.(https://doi.org/10.1038/s41577-020-00464-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Taves MD, Ma C, Heimovics SA, Saldanha CJ & Soma KK 2011 Measurement of steroid concentrations in brain tissue: methodological considerations. Frontiers in Endocrinology 2 39. (https://doi.org/10.3389/fendo.2011.00039)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Taves MD, Plumb AW, Sandkam BA, Ma C, Van Der Gugten JG, Holmes DT, Close DA, Abraham N & Soma KK 2015 Steroid profiling reveals widespread local regulation of glucocorticoid levels during mouse development. Endocrinology 156 511522. (https://doi.org/10.1210/en.2013-1606)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Taves MD, Plumb AW, Korol AM, Van Der Gugten JG, Holmes DT, Abraham N & Soma KK 2016 Lymphoid organs of neonatal and adult mice preferentially produce active glucocorticoids from metabolites, not precursors. Brain, Behavior, and Immunity 57 271281. (https://doi.org/10.1016/j.bbi.2016.05.003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Taves MD, Hamden JE & Soma KK 2017 Local glucocorticoid production in lymphoid organs of mice and birds: functions in lymphocyte development. Hormones and Behavior 88 414. (https://doi.org/10.1016/j.yhbeh.2016.10.022)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Taves MD, Mittelstadt PR, Presman DM, Hager GL & Ashwell JD 2019 Single-cell resolution and quantitation of targeted glucocorticoid delivery in the thymus. Cell Reports 26 36293642. (https://doi.org/10.1016/j.celrep.2019.02.108)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Tobiansky DJ, Kachkovski GV, Enos RT, Schmidt KL, Murphy EA & Soma KK 2020 Sucrose consumption alters steroid and dopamine signalling in the female rat brain. Journal of Endocrinology 245 231246. (https://doi.org/10.1530/JOE-19-0386)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Trottier MD, Newsted MM, King LE & Fraker PJ 2008 Natural glucocorticoids induce expansion of all developmental stages of murine bone marrow granulocytes without inhibiting function. PNAS 105 20282033. (https://doi.org/10.1073/pnas.0712003105)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Vacchio MS & Ashwell JD 1997 Thymus-derived glucocorticoids regulate antigen-specific positive selection. Journal of Experimental Medicine 185 20332038. (https://doi.org/10.1084/jem.185.11.2033)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Vacchio MS, Papadopoulos V & Ashwell JD 1994 Steroid production in the thymus: implications for thymocyte selection. Journal of Experimental Medicine 179 18351846. (https://doi.org/10.1084/jem.179.6.1835)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Vacchio MS, Lee JY & Ashwell JD 1999 Thymus-derived glucocorticoids set the thresholds for thymocyte selection by inhibiting TCR-mediated thymocyte activation. Journal of Immunology 163 13271333.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Van Laethem F, Baus E, Andris F, Urbain J & Leo O 2001 A novel aspect of the anti-inflammatory actions of glucocorticoids: inhibition of proximal steps of signaling cascades in lymphocytes. Cellular and Molecular Life Sciences 58 15991606. (https://doi.org/10.1007/PL00000799)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Walker CD, Akana SF, Cascio CS & Dallman MF 1990 Adrenalectomy in the neonate: adult-like adrenocortical system responses to both removal and replacement of corticosterone. Endocrinology 127 832842. (https://doi.org/10.1210/endo-127-2-832)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Walker CD, Scribner KA, Cascio CS & Dallman MF 1991 The pituitary-adrenocortical system of neonatal rats is responsive to stress throughout development in a time-dependent and stressor-specific fashion. Endocrinology 128 13851395. (https://doi.org/10.1210/endo-128-3-1385)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Walker AK, Nakamura T & Hodgson DM 2010 Neonatal lipopolysaccharide exposure alters central cytokine responses to stress in adulthood in Wistar rats. Stress 13 506515. (https://doi.org/10.3109/10253890.2010.489977)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wei R, Wang J, Su M, Jia E, Chen S, Chen T & Ni Y 2018 Missing value imputation approach for mass spectrometry-based metabolomics data. Scientific Reports 8 663. (https://doi.org/10.1038/s41598-017-19120-0)

    • PubMed
    • Search Google Scholar
    • Export Citation