Androgen skeletal muscle

SBMA In addition to HD, NaBu has also been reported to be effective in treating spinal and bulbar muscular atrophy (SBMA) (Minamiyama et al, 2004), an inheritable motorneuron disease caused by an expanded polyglutamine-repeat within the androgen receptor. SBMA is associated with motorneuron loss in the spinal cord and brain stem as well as a sub-clinical loss of sensory neurons in the dorsal root ganglia resulting in skeletal muscle atrophy and weakness (Sobue et al, 1989 ... 

Finasteride inhibits 5a-reductase, the enzyme converting T. into dihydrotestosterone (DHT). Thus, the androgenic stimulus is reduced in those tissues in which DHT is the active species (e.g., prostate). T.-dependent tissues or functions are not or hardly affected (e.g., skeletal muscle, negative feedback inhibition of gonadotropin secretion, and libido). Finasteride can be used in benign prostate hyperplasia to shrink the gland and, possibly, to improve micturition. 

The protein anabolic actions of androgens on bone and skeletal muscle are responsible for the larger stature of males than females. Androgens induce some degree of anabolism in other tissues, including bone marrow, liver, kidney, and heart. They also have several other actions, not necessarily associated with maleness, such as lymphoid tissue regression during puberty. 

Anabolic activities of testosterone, such as increases in amino acid incorporation into protein and in RNA polymerase activity, have been demonstrated in skeletal muscle. Apart from the direct anabolic effects in specific tissue, androgens antagonize the protein catabolic action of glucocorticoids. The androgen compounds with the greatest ratio of protein anabolic effects to virilizing effects are the 19-nortestosterone derivatives. Compounds that are used clinically (Table 63.3) include nandrolone phenpropionate (Durabolin), nandrolone decanoate... 

D. Skeletal muscle cells use the androgen receptor to bind testosterone that promotes the anabolic effect of this hormone. 

After World War II, anabolic-androgenic steroids (AASs) are given to many starving concentration camp survivors to help them add skeletal muscle and build up body weight. 

The synthetic substances related to the male sex hormones (androgens) are called anabolic steroids . The principal effects of these substances are to promote the growth of skeletal muscle (anabolic effects) and the development of male sexual characteristics (androgenic effects). 

The adrenal cortex, the zona reticularis in particular, daily secretes substantial amounts of DHEA and DHEAS, equaling or exceeding the amount of cortisol. Table 32-1 shows approximate blood levels of the important corticosteroids. Most of the DHEA and all of the DHEAS come from the adrenals. Negligible amounts of testosterone, dihydrotestosterone (DHT), and estradiol are secreted by the cortex however, DHEA and, to a lesser extent, DHEAS undergo conversion to estradiol in skeletal muscle and adipose tissue they also can be converted to testosterone. The adrenal cortex accounts for about two-thirds of the urinary 17-ketosteroids, which are a measure of androgen production. This steroidogenic versatility makes the adrenal cortex an important factor in certain disease states (see below). 

Skeletal Muscle Skeletal muscle has no 5a-reductase, and, although all skeletal muscles are believed to contain AR, some are known to contain a higher concentration than others. The most androgen-responsive skeletal muscle in man (presumably because of a higher concentration of AR) are those of the pectoral and shoulder regions. In other species (e.g., rodents), testosterone promotes skeletal muscle growth by stimulating both hypertrophy and mitosis of myofibrils and increases the fast-twitch isoform... 

These improved pharmacokinetic and side-effect profiles for SARMs versus steroidal androgens are associated with potent, tissue-selective effects in therapeutic target tissues. Hyperanabolic effects in skeletal muscle have been seen for SARMs in rat for numerous molecules [90, 151, 176, 184] with myoanabolic effects in castrated rats in the range of 100-150% compared to testosterone. These effects have also been seen in human trials as manifested by increases in LBM and improvements in physical performance tests (stair climb time [96]). Osteoanabolic effects have also been demonstrated in rats [95, 128, 151] and monkeys [130] for numerous molecules however, only limited clinical trials data have been released in human [128],... 

Androgen receptor Protection against skeletal muscle atrophy Prostate stimulation... 

Sauerwein, H. and Meyer, H.H.D., Androgen and estrogen receptors in bovine skeletal muscle Relation to steroid induced allometric muscle growth, J Anim Sci, 67, 206-212, 1989. 

Inder WJ, Jang C, Obeyesekere VR, Alford FP. Dexamethasone administration inhibits skeletal muscle expression of the androgen receptor and IGF-1—implications for steroid-induced myopathy. Clin Endocrinol 2010 73(1) 126-32. 

Androgen insensitivity syndrome (AIS) Testes and accessory organs of male reproduction (e.g. prostate), skeletal muscles, heart, placenta Xqll-ql2 300068... 

MacLean HE, Chiu WS, Notini AJ et al. (2008) Impaired skeletal muscle development and (unction in male, but not female, genomic androgen receptor knockout mice. FASEB J 22, 2676-2689. 

Ostrowski, J., Kuhns, J.E., Lupisella, J.A., el al. (2006) Pharmacological and x-ray structural characterization of a novel selective androgen receptor modulator potent hyperanabolic stimulation of skeletal muscle with hypostimulation of prostate in rats. Endocrinology, 48,4-12. 

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