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During early development, stress or exogenous glucocorticoid (GC) administration reduces body mass in vertebrates, and this is associated with the glucocorticoid receptor (GR) activation. Although GCs also activate the mineralocorticoid receptor (MR), the physiological significance of MR activation on early developmental growth is unknown. We tested the hypothesis that activation of both GR and MR are required for postnatal growth suppression by GCs. Differential regulation of GR and MR activation was achieved by using ubiquitous GR- (GRKO) and MR- (MRKO) knockout zebrafish (Danio rerio) in combination with exogenous cortisol treatment. MR activation increased protein deposition in zebrafish larvae and also upregulated lepa and downregulated lepr transcript abundance. Cortisol treatment reduced body mass and protein content in the WT, and this corresponded with the upregulation of muscle proteolytic markers, including murf1 and redd1 by GR activation. The combined activation of MR and GR by cortisol also upregulated the gh and igf1 transcript abundance, and insulin expression compared to the WT. However, cortisol-mediated reduction in body mass and protein content required the activation of both MR and GR, as activation by GR alone (MRKO + cortisol) did not reduce the larval protein content. Collectively, our results indicate that MR activation favors protein deposition and GR activation stimulates proteolysis, while their combined activation is involved in cortisol-mediated growth suppression. Overall, this work provides insight into the physiological significance of MR activation in regulating protein deposition during early development at a systems level.
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impairments ( Haffner 2000 , Oh et al . 2002 ). Since skeletal muscle is a major target organ for insulin-regulated glucose metabolism, it is possible that sex hormones may play a significant role in skeletal muscle metabolism and may have distinct sex
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, inflammation is also important in muscle repair after injury ( Tu & Li 2023 ). Figure 2 Effects of the RANKL–RANK pathway on skeletal muscle metabolism. Clinical studies about the effects of the RANKL pathway and its modulation on muscle are
Department of Molecular Biosciences, Department of Nutrition, Department of Pediatrics, Department of Physiology, Division of Endocrinology, School of Veterinary Medicine, University of California Davis, One Shields Avenue, Davis, California 95616, USA
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Department of Molecular Biosciences, Department of Nutrition, Department of Pediatrics, Department of Physiology, Division of Endocrinology, School of Veterinary Medicine, University of California Davis, One Shields Avenue, Davis, California 95616, USA
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. Molecular and Cellular Endocrinology 275 43 – 61 . ( doi:10.1016/j.mce.2007.05.015 ) Weinstein SP Wilson CM Pritsker A Cushman SW 1998 Dexamethasone inhibits insulin-stimulated recruitment of GLUT4 to the cell surface in rat skeletal muscle
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I.N.B.B. (Istituto Nazionale Biostrutture e Biosistemi), Rome, Italy
Andrology, Women’s Endocrinology and Gender Incongruence, Careggi Hospital, Florence, Italy
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I.N.B.B. (Istituto Nazionale Biostrutture e Biosistemi), Rome, Italy
Endocrinology, Careggi Hospital, Florence, Italy
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). Scale bar 500 nm. To further characterize skeletal muscle metabolism, we analyzed the mRNA expression of genes related to insulin sensitivity, lipid and energy metabolism ( Fig. 5 ). We found that TTh induced a significant increase in mRNA
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Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa, USA
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2015 Role of PKCδ in insulin sensitivity and skeletal muscle metabolism . Diabetes 64 4023 – 4032 . ( https://doi.org/10.2337/db14-1891 ) 26307588 10.2337/db14-1891 Liechty EA Boyle DW Moorehead H Liu YM Denne SC 1993 Increased fetal
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KO mice. A similar pattern of Insr expression was observed previously in Cmklr1 KO mice, which also exhibit glucose intolerance ( Ernst et al . 2012 ). Gpr1 loss could also be contributing to dysfunctional skeletal muscle metabolism through
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-adrenergic stimulation of energy expenditure and forearm skeletal muscle metabolism in lean and obese men . American Journal of Physiology 267 E306 – E315 . Blaak EE van Baak MA Kester AD Saris WH 1995 Beta-adrenergically mediated thermogenic and heart
School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, Arizona, USA
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Limesand SW 2012b Developmental programming in response to intrauterine growth restriction impairs myoblast function and skeletal muscle metabolism . Journal of Pregnancy 2012 article 631038 . ( doi:10.1155/2012/631038 ) Yates DT Cadaret CN
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Circulatory Physiology 299 H422 – H430 . ( doi:10.1152/ajpcell.00562.2009 ) Jacob S Henriksen EJ Fogt DL Dietze GJ 1996 Effects of Trandolapril and Verapamil on glucose transport in insulin-resistant rat skeletal muscle . Metabolism
