Glucocorticoid Hormone Stimulates Mitochondrial Biogenesis Specifically in Skeletal Muscle

Abstract

High levels of circulating glucocorticoid hormone may be important mediators for elevating resting metabolic rate upon severe injury or stress. We therefore investigated the effect of dexamethasone on mitochondrial biogenesis in rats (6 mg/kg daily) as well as in cells in culture (1 microM) over a period of 3 d. A marked stimulation of mitochondrial DNA transcription and increased levels of cytochrome c oxidase activity were found in skeletal muscle of rats and differentiated mouse C2C12 muscle cells, but not in other tissues, myoblasts, or other cell lines. The effect was inhibited by RU486. Therefore, increased occupancy of glucocorticoid receptors is necessary, but not sufficient to increase mitochondrial biogenesis and other, skeletal muscle specific factors are postulated. Expression of the mitochondrial transcription factor A was unchanged, suggesting a possible involvement of the recently described mitochondrial glucocorticoid receptor. Expression of uncoupling protein-3 was also unchanged. In conclusion, our results show that high levels of glucocorticoid hormone are sufficient to stimulate mitochondrial biogenesis; however, only in skeletal muscle. Increased mitochondrial mass in this tissue, without changes of the coupling state of the respiratory chain, might be the molecular basis for the elevated resting metabolic rate observed under high cortisol levels in humans.

Ghrelin regulates mitochondrial-lipid metabolism gene expression and tissue fat distribution in liver and skeletal muscle

“…In particular, reported prolactin effects on liver and white adipose tissue lipogenic gene expression and function are opposite to those observed after ghrelin treatment in the current study (1). In addition, excess glucocorticoids are not reported to exert independent effects on hepatic lipogenesis and lipid deposition (14,29,54), whereas most (16,18,30), although not all (55), reports agree on their suppressive or null effect on skeletal muscle mitochondrial function. Thus, taken together, the above observations do not support a major role of additional hypophyseal hormonal changes in observed metabolic effects.…”

Steroid and thyroid hormone receptors in mitochondria

“…However, higher energy requirements demand increased biosynthesis of OXPHOS, increased transcription of OXPHOS genes in the nucleus and in mitochondria, eventually an increase in mitochondrial gene dosage (84,85).…”

CREB-1α Is Recruited to and Mediates Upregulation of the Cytochrome c Promoter during Enhanced Mitochondrial Biogenesis Accompanying Skeletal Muscle Differentiation

“…Indeed, cells are able to adjust energy metabolism by altering the architecture and dynamics of the mitochondrial reticulum (10), by modifying its enzyme equipment and/or the level of proton leak, or by adjusting total mitochondrial respiratory capacity when changes in energy demand persist for long periods (23). Among the factors known to strongly stimulate mitochondrial biogenesis in vivo, the most prominent examples are high levels of thyroid (67) and glucocorticoid (55,66) hormones and also conditions like endurance exercise of muscle (1) and cold adaptation in brown fat tissue (31).…”