Anabolic Effects Of Testosterone Research Articles

Stress Response to Physical Exercise in Rats with Alimentary Obesity.

Stress response to physical exercise was studied in rats with alimentary obesity with and without caloric diet restriction. Daily excretion of corticosterone, progesterone, and testosterone, weights of internal organs, and serum levels of glucose, free fatty acids, triglycerides, corticosterone, and testosterone were estimated. Stress response to moderate exercise in rats with alimentary obesity was associated with predominance of anabolic influence of testosterone over the catabolic effects of corticosterone, which promoted the increase in the weight of reproductive organs. Exposure to physical loads against the background of restricted ration potentiated the response of the adrenocortical system and reduced the concentration and anabolic effects of testosterone.

Síntese proteica em suínos: como fêmeas, machos não castrados e castrados respondem a este processo?

Muscle protein synthesis in pigs can be considered a key factor in promoting lean gain. However, this is a complex process depending on several enzymes, ribosomal proteins and may be affected by environmental factors, besides nutritional and hormonal. In this sense, sexual hormones may have anabolic action in protein synthesis, leading different rates of muscle deposition in barrows, intact males and gilts. Aiming to use the anabolic effect of testosterone, the immunocastration practice is being applied to pig production in many countries, allowing males to show the same growth performance and carcass traits as intact males. In this sense, sex plays an important role on protein synthesis, providing differences in the amino acids requirements, according to its condition (intact males, gilts and barrows) due to differences in carcass protein deposition.

Effects of tail suspension on serum testosterone and molecular targets regulating muscle mass

The contribution of reduced testosterone levels to tail suspension (TS)-induced muscle atrophy remains equivocal. The molecular mechanism by which testosterone regulates muscle mass during TS has not been investigated. Effects of TS on serum testosterone levels, muscle mass, and expression of muscle atrophy- and hypertrophy-inducing targets were measured in soleus (SOL) and extensor digitorum longus (EDL) muscles after testosterone administration during 1, 5, and 14 days of TS in male mice. TS produced an increase followed by a transient drop in testosterone levels. Muscle atrophy was associated with downregulation of Igf1 and upregulation of Mstn, Redd1, Atrogin-1, and MuRF1 mRNA with clear differences in Igf1, Mstn, and MAFbx/Atrogin-1 gene expression between SOL and EDL. Testosterone supplementation did not affect muscle mass or protein expression levels during TS. Conclusions The known anabolic effects of testosterone are not sufficient to ameliorate loss of muscle mass during TS.

The Role of GH and IGF-I in Mediating Anabolic Effects of Testosterone on Androgen-Responsive Muscle

The Role of GH and IGF-I in Mediating Anabolic Effects of Testosterone on Androgen-Responsive Muscle

The Role of GH and IGF-I in Mediating Anabolic Effects of Testosterone on Androgen-Responsive Muscle

The Role of GH and IGF-I in Mediating Anabolic Effects of Testosterone on Androgen-Responsive Muscle

The physiological and pharmacological basis for the ergogenic effects of androgens in elite sports

Androgen doping in power sports is undeniably rampant worldwide. There is strong evidence that androgen administration in men increases skeletal muscle mass, maximal voluntary strength and muscle power. However, we do not have good experimental evidence to support the presumption that androgen administration improves physical function or athletic performance. Androgens do not increase specific force or whole body endurance measures. The anabolic effects of testosterone on the skeletal muscle are mediated through androgen receptor signaling. Testosterone promotes myogenic differentiation of multipotent mesenchymal stem cells and inhibits their differentiation into the adipogenic lineage. Testosterone binding to androgen receptor induces a conformational change in androgen receptor protein, causing it to associate with beta-catenin and TCF-4 and activate downstream Wnt target genes thus promoting myogenic differentiation. The adverse effects of androgens among athletes and recreational bodybuilders are under reported and include acne, deleterious changes in the cardiovascular risk factors, including a marked decrease in plasma high-density lipoproteins (HDL) cholesterol level, suppression of spermatogenesis resulting in infertility, increase in liver enzymes, hepatic neoplasms, mood and behavioral disturbances, and long term suppression of the endogenous hypothalamic-pituitary-gonadal axis. Androgens are often used in combination with other drugs which may have serious adverse events of their own. In spite of effective methods for detecting androgen doping, the policies for screening of athletes are highly variable in different countries and organizations and even existing policies are not uniformly enforced.

Anabolic effects of testosterone in bone of gonadectomized male and female rats

In males (M), testosterone (T) administration augments bone mineral density and maximal bone strength (MBS); however, the direct effects of T‐administration on female (F) bone are less understood. We evaluated the effects of supraphysiological T administration on M and F serum hormone concentrations [T, dihydrotestosterone (DHT), and estradiol (E2)], tibial cancellous bone volume % (CBV%), and femur MBS (3‐point bending test). Fisher SAS rats received Sham surgery + placebo (P), gonadectomy (GNX) + P, or GNX + T (7.0 mg x week‐1) for 28 days. GNX reduced serum T by 99%, DHT by 42–87%, and E2 by 72–82% in both sexes (p<0.05). When compared with Shams, T‐administration resulted in >18‐fold (M) and >100‐fold (F) increases in serum T, 17‐fold (M) and 50‐fold (F) increases in DHT, and a 4‐fold increase in E2 (M) concentrations (p<0.05); while reducing serum E2 by 55% in (F) (p<0.05). T‐administration also reversed the GNX induced reductions in CBV% in M (Sham 4.8±1.0, GNX 1.6±0.5, GNX+T 6.0±0.5; p<0.05) and resulted in a trend towards increased CBV% in F (Sham 9.8±5.7, GNX 3.5±2.6, GNX+T 7.4±3.5; p=0.052), when compared with GNX. Ultimately, GNX+T augmented MBS by ~6–12% in M and ~15–19% in F when compared with Sham and GNX, respectively (p<0.05). Our results indicate that supraphysiological T‐administration directly augments CBV% and MBS after GNX in both M and F rats. Study funded by VA Merit grant (S.E. Borst).

Anabolic effects of testosterone are preserved during inhibition of 5α-reductase

At replacement doses, testosterone produces only modest increases in muscle strength and bone mineral density in older hypogonadal men. Although higher doses of testosterone are more anabolic, there is concern over increased adverse effects, notably prostate enlargement. We tested a novel strategy for obtaining robust anabolic effects without prostate enlargement. Orchiectomized (ORX) male rats were treated for 56 days with 1.0 mg testosterone/day, with and without 0.75 mg/day of the 5alpha-reductase inhibitor MK-434. Testosterone administration elevated the prostate dihydrotestosterone concentration and caused prostate enlargement. Both effects were inhibited by MK-434. ORX produced a catabolic state manifested in reduced food intake, blunted weight gain, reduced hemoglobin concentration, decreased kidney mass, and increased bone resorption, and in the proximal tibia there was both decreased cancellous bone volume and a decreased number of trabeculae. In soleus and extensor digitorum longus muscles, ORX reduced both the percentage of type I muscle fibers and the cross-sectional area of type 1 and 2 fibers. Testosterone administration caused a number of anabolic effects, including increases in food intake, hemoglobin concentration, and grip strength, and reversed the catabolic effects of ORX on bone. Testosterone administration also partially reversed ORX-induced changes in muscle fibers. In contrast to the prostate effects of testosterone, the effects on muscle, bone, and hemoglobin concentration were not blocked by MK-434. Our study demonstrates that the effects of testosterone on muscle and bone can be separated from the prostate effects and provides a testable strategy for combating sarcopenia and osteopenia in older hypogonadal men.

A Selective Androgen Receptor Modulator for Hormonal Male Contraception

The recent discovery of nonsteroidal selective androgen receptor modulators (SARMs) provides a promising alternative for testosterone replacement therapies, including hormonal male contraception. The identification of an orally bioavailable SARM with the ability to mimic the central and peripheral androgenic and anabolic effects of testosterone would represent an important step toward the "male pill". We characterized the in vitro and in vivo pharmacologic activity of (S)-3-(4-chloro-3-fluorophenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethylphenyl)propionamide (C-6), a novel SARM developed in our laboratories. C-6 was identified as an androgen receptor (AR) agonist with high AR binding affinity (K(i) = 4.9 nM). C-6 showed tissue-selective pharmacologic activity with higher anabolic activity than androgenic activity in male rats. The doses required to maintain the weight of the prostate, seminal vesicles, and levator ani muscle to half the size of the maximum effects (i.e., ED(50)) were 0.78 +/- 0.06, 0.88 +/- 0.1, and 0.17 +/- 0.04 mg/day, respectively. As opposed to other SARMs, gonadotropin levels in C-6-treated groups were significantly lower than control values. C-6 also significantly decreased serum testosterone concentration in intact rats after 2 weeks of treatment. Marked suppression of spermatogenesis was observed after 10 weeks of treatment with C-6 in intact male rats. Pharmacokinetic studies of C-6 in male rats revealed that C-6 was well absorbed after oral administration (bioavailability 76%), with a long (6.3 h) half-life at a dose of 10 mg/kg. These studies show that C-6 mimicked the in vivo pharmacologic and endocrine effects of testosterone while maintaining the oral bioavailability and tissue-selective actions of nonsteroidal SARMs.

Role of IGF-I and IGF-binding proteins within diaphragm muscle in modulating the effects of nandrolone.

Recent studies suggest that the anabolic effects of testosterone in muscle may be mediated, in part, by the insulin-like growth factor (IGF) system. The aim of this study was to examine the effects of nandrolone (NAN) on both IGF-I and IGF-binding proteins (IGFBPs) in the diaphragm muscle of 1-yr-old female rats. NAN (6.6 mg. kg(-1) x day(-1)) was infused continuously for 17 days using a subcutaneous Silastic implant, whereas controls (CTL) received blank capsules. Muscle fibers were classified immunohistochemically, and fiber cross-sectional areas (CSA) were determined quantitatively. IGF-I levels in both serum and muscle were determined by RIA. Immunoreactivity to an IGF-I antibody was used to localize IGF-I expression within individual muscle fibers. Muscle IGFBPs were determined by SDS-PAGE and Western ligand blotting and measured by scanning densitometry. Body weight was higher in the NAN group compared with CTL (9.4 +/- 4.5% vs. -0.6 +/- 3.1%). There were no changes in the fiber composition of the diaphragm. NAN increased the CSA of type IIa (20%) and type IIx/b (30%) diaphragm fibers. Levels of IGF-I in the diaphragm muscle were significantly higher (50%) in NAN-treated animals. Immunohistochemistry revealed increased localization of IGF-I within type IIx/b diaphragm fibers. In addition, NAN increased IGFBP-3 within the diaphragm (69%), whereas IGFBP-4 decreased (40%). We conclude that NAN-induced diaphragm muscle fiber hypertrophy is mediated, in part, by influences of the IGF system within the muscle, such that coordinated changes in IGFBPs reflect a direction of change that has been associated with an anabolic response in other test systems.

Estrogens do not affect whole-body protein metabolism in the prepubertal female.

The increase in bone mass, muscle bulk, and linear growth that occur during puberty are mediated, at least in part, through the action of sex steroids. By using infusions of nonradioactive tracers of leucine, we have recently shown a significant protein anabolic effect of testosterone in prepubertal boys. The present study was designed to determine whether estrogens can cause similar changes in protein metabolism in females. Seven prepubertal girls (Turner's syndrome, n = 6; hypogonadotropism, n = 1; mean age 12.2 +/- 0.3 yr) were studied. A 4-h infusion of L(-)[1-(13C)]leucine was given, and the isotopic enrichment of [13C]ketoisocaproic acid and 13CO2 were measured in plasma and in breath with use of gas chromatography/mass spectroscopy and an isotope ratio mass spectrometer, respectively. The reciprocal pool model was used for analysis of leucine kinetics. Subjects were then started on ethinyl estradiol orally (n = 5) or depot estradiol parenterally (n = 2). An identical study was repeated 4 weeks later. There were comparable changes in leucine kinetics in all girls studied, hence their data were grouped for analysis. After administration of ethinyl estradiol, there were insignificant changes in the rate of appearance of leucine, an index of proteolysis (+6% +/- 8%); leucine oxidation (-9% +/- 11%); and nonoxidative leucine disposal, an index of whole body protein synthesis (+10% +/- 8%). This is in sharp contrast to the changes found in boys studied similarly after treatment with testosterone (rate of appearance: 17 +/- 6%, P = .036; leucine oxidation -49 +/- 5%, P = 0.004; and nonoxidative leucine disposal +35 +/- 8%, P = 0.009). The lack of anabolic effect on whole-body protein in the girls reported here was observed despite significant increases in plasma insulin-like growth factor I concentrations during 4 h of sampling when comparing the 2 study days, similar to that of the prepubertal boys who were treated with testosterone. In summary, we observed that contrary to androgens, estrogens do not alter estimates of whole-body protein turnover and anabolism in prepubertal humans, despite significant increases in circulating insulin-like growth factor I concentrations. In conclusion, the impact of testosterone on protein metabolism seems to be a direct effect of androgens, independent of aromatization. These findings correlate with the significant differences in muscle bulk between the sexes as children go through puberty.

Effect of testosterone on whole body amino acid utilization in myotonic dystrophy

Patients with myotonic dystrophy are markedly insulin resistant and have an associated abnormality in the regulation of arterialized amino acid concentrations during euglycemic insulin infusions. We studied the effect of testosterone treatment on whole body amino acid balance in myotonic dystrophy, since it increases muscle mass and muscle protein synthesis rate. Six patients with myotonic dystrophy underwent studies of glucose disposal and amino acid regulation during low dose insulin infusions with maintenance of euglycemia, prior to and after 10 to 13 weeks of testosterone (3 mg/kg/wk). Testosterone increased the insulin-stimulated decline of certain amino acids, but did not improve whole body glucose uptake. The anabolic effect of testosterone is separate from the anabolic effect of insulin.

Actions of Androgens on the Kidney of Female Mice: Strain Differences in the DNA and β‐Glucuronidase Responses

The anabolic effects of testosterone on kidneys from two strains of female mice were studied over a course of 25 days. The A/J and C57BL/6J strains were selected because they carry regulatory alleles Gura and Gurb which determine rapid and slow induction of β‐glucuronidase, respectively. (A major goal of this study was to determine whether these mouse strains have other differences in their responses to testosterone). The wet weight, dry weight and total protein content of the kidneys of both strains increased about 70% in both strains. Total RNA increased 112% and 93% in a biphasic manner in the A/J and C57BL/6J mouse strains, respectively. The steep slope during the first 5 to 7 days was attributed to a selective stimulation of RNA accumulation while the latter, less rapid, RNA increase occurred in parallel with tissue growth. The total DNA content of kidneys from testosterone treated A/J mice never increased above that of controls, indicating that hypertrophy could account for renal enlargement in this strain. By contrast, testosterone treatment produced a 24% increase in total kidney DNA in C57BL/6J mice, signifying that both hypertrophy and hyperplasia are important factors in the anabolic response of this strain. These observations indicated another difference in the androgen induced response of A/J and C57BL/6J mice.As a consequence of the testosterone stimulated increase in renal β‐glucu‐ronidase synthesis, the excretion of the lysosomal form of the enzyme into the urine increased 2200‐fold in A/J but only 57‐fold in C57BLIGJ. The total enzyme activity excretedidayimouse was only 4 times higher in A/J versus C57BLi6J with the differences reflecting the basal activity which was 10‐fold higher in C57BLIGJ mice. The basal excretion of another lysosomal enzyme, β‐galactosidase, was also several fold higher in C57BL/6J, suggesting that lysosomes in those animals are either larger or their contents are excreted at a faster rate.

Anabolic effect of testosterone on the levator ani muscle of the rat.

1. The effect of testosterone on the weight and on the contractile, histochemical and electrophysiological properties of the levator ani (LA) muscle and other skeletal muscles of non-castrated rats was studied. 2. Administration of testosterone for 12 days resulted in a more than two-fold increase of the weight of LA muscle and in increased muscle fibre diameter. Contraction time and other parameters of the twitch were markedly shortened. Twitch tension as well as maximum tetanic tension increased, in the latter case up to 250% of the control values. A similar, but less pronounced anabolic effect on the LA muscle was also observed after 30 days of testosterone administration. 3. No change in the muscle fibre pattern of ATP-ase activity was found in the LA muscle after long-term testosterone treatment. 4. Resting membrane potential of LA muscle fibres increased after 30 days of testosterone administration from 74–83 mV. Increase of resting potential was blocked only partially by 2×10−5 M ouabain in vitro. 5. LA muscle fibres from testosterone treated rats showed a 60% increase of input membrane resistance and a lower rate of sodium permeability activation during action potential generation. 6. Frequency of miniature end-plate potentials in LA muscles of rats treated for 12 and 30 days decreased to about one third of control values. 7. No similar changes of weight, contraction and electrophysiological properties were found in the soleus, extensor digitorum longus and diaphragm muscles of rats treated with testosterone for 12 and 30 days respectively.

Anabolic effect of dihydrotestosterone in testicular feminization syndrome

Patients with testicular feminization syndrome (TFS) are unresponsive to the masculinizing and anabolic effects of testosterone (T). Conversion of T to dihydrotesterone (DHT) and the binding of these steroids to nuclear chromatin appear to be related to end-organ responsiveness to T. Defective conversion of T to DHT has been observed in TFS. Three siblings with TFS were studied before and after gonadectomy to assess their responsiveness to the anabolic effects of DHT. Daily 24 hr urine nitrogen and phosphorus were measured under metabolic balance conditions before and during DHT administration. Two hypogonadal male patients served as controls. Significant reductions in urinary nitrogen and positive nitrogen balance during DHT were observed in both TFS patients studied prior to gonadectomy. This response was less than that of the controls. Two patients were unresponsive to DHT 3 mo postgonadectomy. Defective conversion of T to DHT would not explain this unresponsiveness of TFS patients to DHT. A more plausable explanation is a deficient affinity of nuclear receptor sites for androgenic steroids. The limited response to DHT in the intact state may be due to summation of endogenous and exogenous androgens or to participation of estrogen in the anabolic response.

Comparative androgenic and anabolic effects of several steroids.

SummaryThe androgenic and anabolic effects of testosterone, testosterone propionate, methyl testosterone, methyl androstenediol, androstanolone and 17-ethyl-19-nortestosterone (Nilevar) were compared. The greatest androgenic responses were obtained with testosterone propionate while the most marked anabolic effects were observed with either testosterone propionate or 17-ethyl-19-nortestosterone. Compared to testosterone propionate, methyl androstenediol and androstanolone showed a small increase in the anabolic: androgenic potency ratio but a much more marked increase was observed with 17-ethyl-19-nortestosterone.

Effect of intravenous testosterone on nitrogen balance in man.

The anabolic effect of testosterone and its analogues has been adequately demonstrated by many workers. More recently, a preparation of testosterone dissolved in a solution of 25 per cent human serum albumin for intravenous administration was studied in our laboratories (1). This preparation was administered intravenously to 4 subjects and appeared to stimulate a sustained anabolic response in the 2 who received more than 150 mg. of the hormone.

Rates of protein synthesis, amino acid catabolism and size of nitrogen pool during nitrogen storage induced with testosterone propionate, and testosterone propionate combined with growth hormone.

In the human, normal growth appears to occur in two phases: prepuberal growth, hypothesized as being entirely referable to pituitary growth hormone, and puberal growth referable to steroid growth promoting factors from the gonads and the adrenal cortex (Kinsell et at., 1948). Nitrogen retention and protein anabolic effects of testosterone and its derivatives, methyltestosterone and particularly testosterone propionate have received considerable attention, and, although much factual information has been obtained (Kochakian, 1946, 1950), elucidation of the mechanism of these effects is still awaited. Technical procedures and mathematical treatment developed by Sprinson and’Rittenberg (1949) and Hoberman (1949–50) for assessing protein and amino acid metabolism in terms of rates of protein synthesis, amino acid catabolism, and size of the nitrogen pool have been utilized in characterizing and quantitating the over-all mechanisms involved in nitrogen storage induced in the adult female dog with anterior pitui...