Isoflurane stress induces glucocorticoid production in mouse lymphoid organs

in Journal of Endocrinology
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  • 1 Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada
  • | 2 Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada
  • | 3 Department of Psychology, University of British Columbia, Vancouver, British Columbia, Canada
  • | 4 Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
  • | 5 Graduate Program in Neuroscience, University of British Columbia, Vancouver, British Columbia, Canada

Correspondence should be addressed to K K Soma: ksoma@psych.ubc.ca
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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.

 

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