Davies, KL;
Camm, EJ;
Smith, DJ;
Vaughan, OR;
Forhead, AJ;
Murray, AJ;
Fowden, AL;
(2021)
Glucocorticoid maturation of mitochondrial respiratory capacity in skeletal muscle before birth.
Journal of Endocrinology
, 251
(1)
pp. 53-68.
10.1530/JOE-21-0171.
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Abstract
In adults, glucocorticoids act to match the supply and demand for energy during physiological challenges, partly through actions on tissue mitochondrial oxidative phosphorylation (OXPHOS) capacity. However, little is known about the role of the natural prepartum rise in fetal glucocorticoid concentrations in preparing tissues for the increased postnatal energy demands. This study examined the effe ct of manipulating cortisol concentrations in fetal sheep during late gestation on mitochondrial OXPHOS capacity of two skeletal muscles with different postnatal locomo tive functions. Mitochondrial content, biogenesis markers, respiratory rates and expression of proteins and genes involved in the electron transfer system (ETS) and OX PHOS efficiency were measured in the biceps femoris (BF) and superficial digital flexor (SDF) of fetuses either infused with cortisol before the prepartum rise or adrenalectomised to prevent this increment. Cortisol infusion increased mitochondrial content, biogenesis markers, substrate-specific respiration rates and abundance of ETS comple x I and adenine nucleotide translocator (ANT1) in a muscle-specific manner that was more pronounced in the SDF than BF. Adrenalectomy reduced mitochondrial content and expression of PGC1? and ANT1 in both muscles, and ETS complex IV abundance in the SDF near term. Uncoupling protein gene expression was unaffected by cortisol ma nipulations in both muscles. Gene expression of the myosin heavy chain isoform, MHCIIx, was increased by cortisol infusion and reduced by adrenalectomy in the BF alo ne. These findings show that cortisol has a muscle-specific role in prepartum matur ation of mitochondrial OXPHOS capacity with important implications for the health of neonates born pre-Term or after intrauterine glucocorticoid overexposure.
| Type: | Article |
|---|---|
| Title: | Glucocorticoid maturation of mitochondrial respiratory capacity in skeletal muscle before birth |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1530/JOE-21-0171 |
| Publisher version: | https://doi.org/10.1530/JOE-21-0171 |
| Language: | English |
| Additional information: | © The authors 2021.This work is licensed under a Creative Commons Attribution 4.0 International License |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Endocrinology & Metabolism, mitochondria, cortisol, maturation, fetus, OXIDATIVE-PHOSPHORYLATION, THYROID-HORMONES, FETAL, CORTISOL, FIBERS, GROWTH, SHEEP, DEXAMETHASONE, BIOGENESIS, METABOLISM |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Maternal and Fetal Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10150523 |
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