Orx animal11/27/2022 Treatment with anti-androgens limits gains in muscle strength during weight training ( Ruzic et al. 2001) and produces ultrastructural signs of degeneration and reduced protein synthesis ( Ustunel et al. Nevertheless, castration in rats reduces contractile force in muscles of the hindlimb ( Brown et al. AR is detectable in bone and muscle cells, but levels are low compared with reproductive tissues such as the prostate and levator ani muscle ( Antonio et al. The mechanisms by which androgens promote anabolism in adult animals are largely unknown. Thus, restoring androgens to youthful levels could potentially be used to manage sarcopenia, osteoporosis, visceral obesity, and frailty. Treatment with testosterone improves muscle mass and strength, bone density, and reduces visceral fat in a variety of subjects ( Bardin 1996, Katznelson et al. 1999), increased visceral fat ( Katznelson et al. This loss of endogenous androgens parallels several symptoms of aging, including decreased muscle mass and function ( Snyder et al. After reaching peak levels in early adulthood, androgen levels decline with age in both sexes ( Tenover 1994, Lamberts et al. Both testosterone and DHT activate the androgen receptor (AR), a nuclear receptor that functions as a transcription factor in hormone-sensitive cells ( Chang et al. Testosterone, the major circulating androgen, can act directly or be converted to the more potent androgen 5α-dihydrotestosterone (DHT) by 5α-reductase, or to estrogens by aromatase ( Russell & Wilson 1994, Simpson et al. Thus, we propose that androgenic anabolism involves early downregulation of Axin and induction of IGF1, leading to nuclear accumulation of β-catenin, a pro-myogenic, anti-adipogenic stem cell regulatory factor.Īndrogens are important endocrine regulators of male sexual development and maintenance of muscle, bone, adipose tissue, and body composition ( Vermeulen 1998, Vermeulen et al. Likewise, treatment of C2C12 myoblasts with both IGF1Ea and MGF C-terminal peptide increased nuclear β-catenin in vitro. DHT increased total levels of β-catenin protein, which accumulated in nuclei in vivo. Interestingly, Axin and Axin2, negative regulators of β-catenin, were repressed, indicating modulation of the β-catenin pathway. Of 24 000 genes examined, 70 candidate genes were identified whose functions suggest initiation of remodeling and regeneration, including the type II muscle genes for myosin heavy chain type II and parvalbumin and the chemokine monocyte chemoattractant protein-1. A genome-wide microarray screen was also performed to identify potential pro-myogenic genes that respond to androgen receptor activation in vivo within 24 h. During the first week, DHT transiently increased soleus muscle nuclear density and induced expression of IGF1 and its splice variant mechano growth factor (MGF) without early regulation of the myogenic factors MyoD, myogenin, monocyte nuclear factor, or myostatin. Treatment with testosterone or 5α-dihydrotestosterone (DHT) reverses the effects on muscle and adipose tissues while only aromatizable testosterone increased bone mass. Here, we demonstrate that aged castrated rats develop increased fat mass, reduced muscle mass and strength, and lower bone mass. Circulating androgens decline with age, contributing to frailty, osteoporosis, and obesity however, the mechanisms by which androgens modulate body composition are largely unknown. Androgens promote anabolism in the musculoskeletal system while generally repressing adiposity, leading to lean body composition.
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