Tissue-specific expression of 11β-HSD and its effects on plasma corticosterone during the stress response
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Tissue-specific expression of 11β-HSD and its effects on plasma corticosterone during the stress response. / Perez, Jonathan H.; Swanson, Ryan E.; Lau, Hannah J.; Cheah, Jeffrey; Bishop, Valerie R.; Snell, Katherine R. S.; Reid, Angus M. A.; Meddle, Simone L.; Wingfield, John C.; Krause, Jesse S.
In: Journal of Experimental Biology, Vol. 223, No. 1, 209346, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Tissue-specific expression of 11β-HSD and its effects on plasma corticosterone during the stress response
AU - Perez, Jonathan H.
AU - Swanson, Ryan E.
AU - Lau, Hannah J.
AU - Cheah, Jeffrey
AU - Bishop, Valerie R.
AU - Snell, Katherine R. S.
AU - Reid, Angus M. A.
AU - Meddle, Simone L.
AU - Wingfield, John C.
AU - Krause, Jesse S.
PY - 2020
Y1 - 2020
N2 - The hypothalamic-pituitary-adrenal (HPA) axis is under complex regulatory control at multiple levels. Enzymatic regulation plays an important role in both circulating levels of glucocorticoids and target tissue exposure. Three key enzyme pathways are responsible for the immediate control of glucocorticoids. De novo synthesis of glucocorticoid from cholesterol involves a multistep enzymatic cascade. This cascade terminates with 11 beta-hydroxylase, responsible for the final conversion of 11-deoxy precursors into active glucocorticoids. Additionally, 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) controls regeneration of glucocorticoids from inactive metabolites, providing a secondary source of active glucocorticoids. Localized inactivation of glucocorticoids is under the control of Type 2 11 beta-HSD (11 beta-HSD2). The function of these enzymes is largely unexplored in wild species, particularly songbirds. Here, we investigated the contribution of both clearance and generation of glucocorticoids to regulation of the hormonal stress response via the use of pharmacological antagonists. Additionally, we mapped 11 beta-HSD gene expression. We found 11 beta-HSD1 primarily in liver, kidney and adrenal glands, although it was detectable across all tissue types. 11 beta-HSD2 was predominately expressed in the adrenal glands and kidney with moderate gonadal and liver expression. Inhibition of glucocorticoid generation by metyrapone was found to decrease levels peripherally, while both peripheral and central administration of the 11 beta-HSD2 inhibitor DETC resulted in elevated concentrations of corticosterone. These data suggest that during the stress response, peripheral antagonism of the 11 beta-HSD system has a greater impact on circulating glucocorticoid levels than central control. Further studies should aim to elucidate the respective roles of the 11 beta-HSD and 11 beta-hydroxylase enzymes.
AB - The hypothalamic-pituitary-adrenal (HPA) axis is under complex regulatory control at multiple levels. Enzymatic regulation plays an important role in both circulating levels of glucocorticoids and target tissue exposure. Three key enzyme pathways are responsible for the immediate control of glucocorticoids. De novo synthesis of glucocorticoid from cholesterol involves a multistep enzymatic cascade. This cascade terminates with 11 beta-hydroxylase, responsible for the final conversion of 11-deoxy precursors into active glucocorticoids. Additionally, 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) controls regeneration of glucocorticoids from inactive metabolites, providing a secondary source of active glucocorticoids. Localized inactivation of glucocorticoids is under the control of Type 2 11 beta-HSD (11 beta-HSD2). The function of these enzymes is largely unexplored in wild species, particularly songbirds. Here, we investigated the contribution of both clearance and generation of glucocorticoids to regulation of the hormonal stress response via the use of pharmacological antagonists. Additionally, we mapped 11 beta-HSD gene expression. We found 11 beta-HSD1 primarily in liver, kidney and adrenal glands, although it was detectable across all tissue types. 11 beta-HSD2 was predominately expressed in the adrenal glands and kidney with moderate gonadal and liver expression. Inhibition of glucocorticoid generation by metyrapone was found to decrease levels peripherally, while both peripheral and central administration of the 11 beta-HSD2 inhibitor DETC resulted in elevated concentrations of corticosterone. These data suggest that during the stress response, peripheral antagonism of the 11 beta-HSD system has a greater impact on circulating glucocorticoid levels than central control. Further studies should aim to elucidate the respective roles of the 11 beta-HSD and 11 beta-hydroxylase enzymes.
KW - Glucocorticoid
KW - Corticosterone
KW - Hypothalamic-pituitaryadrenal axis
KW - HPA axis
KW - 11 beta-HSD
KW - Negative feedback
KW - Songbird
KW - Stress
KW - 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-2
KW - SEASONAL-CHANGES
KW - HOUSE SPARROW
KW - BRAIN
KW - RECEPTORS
KW - GLUCOCORTICOIDS
KW - LOCALIZATION
KW - INHIBITION
KW - METABOLISM
KW - BEHAVIOR
U2 - 10.1242/jeb.209346
DO - 10.1242/jeb.209346
M3 - Journal article
C2 - 31796607
VL - 223
JO - Journal of Experimental Biology
JF - Journal of Experimental Biology
SN - 0022-0949
IS - 1
M1 - 209346
ER -
ID: 247448126