Modulation of Follistatin and Myostatin Propeptide by Anabolic Steroids and Gender

Mosler, Stephanie; Geisler, Stephan; Hengevoß, Jonas; Schiffer, Thorsten; Marion, P; Adler, Michael; Diel, Patrick

doi:10.1055/s-0032-1312585

Cited by 9 publications

(6 citation statements)

References 25 publications

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“…Strikingly, our gene array analysis revealed that transcript levels of Mstn were reduced Ͼ6-fold in satARKO LA muscle, which was confirmed by quantitative real-time PCR, Western blot, and on orx and T and DHT supplementation in WT mice. This positive regulation of Mstn expression by androgens is in accordance with the lower serum Mstn levels recorded in female compared to male subjects (54) and the increase in serum Mstn concentration observed on T treatment of both young and older men (55). Androgen regulation of Mstn was not restricted to LA muscle, in line with previous rodent orx and androgen treatment studies (56 -58).…”

Section: Discussionsupporting

confidence: 90%

A satellite cell‐specific knockout of the androgen receptor reveals myostatin as a direct androgen target in skeletal muscle

et al. 2014

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Androgens have well-established anabolic actions on skeletal muscle, although the direct effects of the androgen receptor (AR) in muscle remain unclear. We generated satellite cell-specific AR-knockout (satARKO) mice in which the AR is selectively ablated in satellite cells, the muscle precursor cells. Total-limb maximal grip strength is decreased by 7% in satARKO mice, with soleus muscles containing ∼10% more type I fibers and 10% less type IIa fibers than the corresponding control littermates. The weight of the perineal levator ani muscle is markedly reduced (-52%). Thus, muscle AR is involved in fiber-type distribution and force production of the limb muscles, while it is a major determinant of the perineal muscle mass. Surprisingly, myostatin (Mstn), a strong inhibitor of skeletal muscle growth, is one of the most androgen-responsive genes (6-fold reduction in satARKO) through direct transcription activation by the AR. Consequently, muscle hypertrophy in response to androgens is augmented in Mstn-knockout mice. Our finding that androgens induce Mstn signaling to restrain their own anabolic actions has implications for the treatment of muscle wasting disorders.-Dubois, V., Laurent, M. R., Sinnesael, M., Cielen, N., Helsen, C., Clinckemalie, L., Spans, L., Gayan-Ramirez, G., Deldicque, L., Hespel, P., Carmeliet, G., Vanderschueren, D., and Claessens, F. A satellite cell-specific knockout of the androgen receptor reveals myostatin as a direct androgen target in skeletal muscle.

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Section: Discussionsupporting

confidence: 90%

A satellite cell‐specific knockout of the androgen receptor reveals myostatin as a direct androgen target in skeletal muscle

et al. 2014

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“…Indeed, in a previous study in humans, we detected gender differences in myostatin propeptide and follistatin concentrations (Mosler et al. ). Also McMahon et al.…”

Section: Discussionmentioning

confidence: 99%

Combinatory effects of siRNA-induced myostatin inhibition and exercise on skeletal muscle homeostasis and body composition

et al. 2014

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Inhibition of myostatin (Mstn) stimulates skeletal muscle growth, reduces body fat, and induces a number of metabolic changes. However, it remains unexplored how exercise training modulates the response to Mstn inhibition. The aim of this study was to investigate how siRNA‐mediated Mstn inhibition alone but also in combination with physical activity affects body composition and skeletal muscle homeostasis. Adult mice were treated with Mstn‐targeting siRNA and subjected to a treadmill‐based exercise protocol for 4 weeks. Effects on skeletal muscle and fat tissue, expression of genes, and serum concentration of proteins involved in myostatin signaling, skeletal muscle homeostasis, and lipid metabolism were investigated and compared with Mstn −/− mice. The combination of siRNA‐mediated Mstn knockdown and exercise induced skeletal muscle hypertrophy, which was associated with an upregulation of markers for satellite cell activity. SiRNA‐mediated Mstn knockdown decreased visceral fat and modulated lipid metabolism similar to effects observed in Mstn −/− mice. Myostatin did not regulate its own expression via an autoregulatory loop, however, Mstn knockdown resulted in a decrease in the serum concentrations of myostatin propeptide, leptin, and follistatin. The ratio of these three parameters was distinct between Mstn knockdown, exercise, and their combination. Taken together, siRNA‐mediated Mstn knockdown in combination with exercise stimulated skeletal muscle hypertrophy. Each intervention or their combination induced a specific set of adaptive responses in the skeletal muscle and fat metabolism which could be identified by marker proteins in serum.

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“…Smoke decreases myostatin levels, while it was not dependent on current PA, parathyroid hormone (PTH), testosterone, and 17β-estradiol (31,34). Pro-myostatin is not affected by menstrual cycle (35) and females have slightly lower levels compared to males (25). High plasma levels of myostatin were found in in rats with chronic kidney disease (CKD) (36) and in patients with chronic obstructive pulmonary disease (COPD) (37).…”

Section: Pre-analytical Factorsmentioning

confidence: 99%

Measuring myokines with cardiovascular functions: pre-analytical variables affecting the analytical output

Lombardi¹,

Sansoni²,

Banfi³

2017

Ann. Transl. Med.

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Abstract:In the last few years, a growing number of molecules have been associated to an endocrine function of the skeletal muscle. Circulating myokine levels, in turn, have been associated with several pathophysiological conditions including the cardiovascular ones. However, data from different studies are often not completely comparable or even discordant. This would be due, at least in part, to the whole set of situations related to the preparation of the patient prior to blood sampling, blood sampling procedure, processing and/or store. This entire process constitutes the pre-analytical phase. The importance of the preanalytical phase is often not considered. However, in routine diagnostics, the 70% of the errors are in this phase. Moreover, errors during the pre-analytical phase are carried over in the analytical phase and affects the final output. In research, for example, when samples are collected over a long time and by different laboratories, a standardized procedure for sample collecting and the correct procedure for sample storage are acknowledged. In this review, we discuss the pre-analytical variables potentially affecting the measurement of myokines with cardiovascular functions.

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Modulation of Follistatin and Myostatin Propeptide by Anabolic Steroids and Gender

Cited by 9 publications

References 25 publications

A satellite cell‐specific knockout of the androgen receptor reveals myostatin as a direct androgen target in skeletal muscle

A satellite cell‐specific knockout of the androgen receptor reveals myostatin as a direct androgen target in skeletal muscle

Combinatory effects of siRNA-induced myostatin inhibition and exercise on skeletal muscle homeostasis and body composition

Measuring myokines with cardiovascular functions: pre-analytical variables affecting the analytical output

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