Heavy resistance exercise training and skeletal muscle androgen receptor expression in younger and older men

Effects of heavy resistance exercise on serum testosterone and skeletal muscle androgen receptor (AR) concentrations were examined before and after a 21-week resistance training period. Seven healthy untrained young adult men (YT) and ten controls (YC) as well as ten older men (OT) and eight controls (OC) volunteered as subjects. Heavy resistance exercise bouts (5 × 10 RM leg presses) were performed before and after the training period. Muscle biopsies were obtained before and 1h and 48 h after the resistance exercise bouts from m.vastus lateralis (VL) to determine cross-sectional area of muscle fibers (fCSA) and AR mRNA expression and protein concentrations. No changes were observed in YC and OC while resistance training led to significant increases in maximal strength of leg extensors (1 RM), fCSA and lean body mass in YT and OT. Acute increases occurred in serum testosterone concentrations due to resistance exercises but basal testosterone remained unaltered. Mean AR mRNA expression and protein concentration remained unchanged after heavy resistance exercise bouts compared to pre-values. The individual pre- to post-training changes in resting (pre-exercise) AR protein concentration correlated with the changes in fCSA and lean body mass in the combined group of YT and OT. Similarly, it correlated with the changes in 1 RM in YT. Although mean AR expression did not changed due to the resistance exercise training, the present findings suggest that the individual changes of AR protein concentration in skeletal muscle following resistance training may have an impact on training-induced muscular adaptations in both younger and older men.     

Recovery after heavy resistance exercise and skeletal muscle androgen receptor and insulin-like growth factor-I isoform expression in strength trained men

The effects of heavy resistance exercise on skeletal muscle androgen receptor (AR) protein concentration and mRNAs of AR, insulin-like growth factor-I (IGF)-IEa, and mechano growth factor (MGF) expression were examined from biopsies of vastus lateralis (VL) muscle before and 48 hours after heavy resistance exercise (5 × 10 repetition maximum [RM] leg press and 4 × 10RM squats) in 8 adult strength trained men. The present exercise induced an acute decrease in maximal isometric force and increased serum total testosterone (T) and free testosterone (FT) concentrations. During 2 recovery days, maximal isometric force and subjective perception of physical fitness remained significantly lowered, whereas serum creatine kinase activity, subjective muscle soreness, and muscle swelling (i.e., thickness of VL by ultrasound) were significantly increased compared to pre-exercise values. Subjective perception of physical fitness was followed up to 7 days, and by 6 days postexercise, it was elevated above the pre-exercise level. Basal T and FT concentrations remained unaltered after the exercise. No statistically significant changes were observed in AR protein or mRNA expression, but IGF-IEa (p < 0.05) and MGF (p < 0.05) mRNA expression were increased compared to pre-exercise levels. These findings indicate that IGF-IEa and MGF responses may be related to acute regenerative processes in muscle because of exercise and may contribute to muscular adaptation to resistance exercise. Subjective perception of physical fitness suggests that recovery over a pre-exercise level of the present type of heavy resistance exercise can take approximately 6 days.     

Androgen receptors and testosterone in men--effects of protein ingestion, resistance exercise and fiber type

The purpose of this study was to examine the impact of protein ingestion on circulating testosterone and muscle androgen receptor (AR) as well as on insulin-like growth factor-I (MGF and IGF-IEa) responses to a resistance exercise (RE) bout in (57-72 year) men. Protein (15 g whey) (n=9) or placebo (n=9) was consumed before and after a RE bout (5 sets of 10 repetition maximums), and vastus lateralis muscle biopsies were taken pre, 1 and 48 h post-RE. The protein ingestion blunted the RE-induced increase in serum free and total testosterone while the RE bout significantly increased muscle AR mRNA levels in older men (P<0.05). However, protein ingestion did not significantly affect AR mRNA or protein expression, or MGF and IGF-IEa mRNA expression at 1 and 48 h post-RE. Immunohistochemical staining of muscle cross-sections was done with antibodies specific to AR and MyHC I and II and showed that there seems to be within or near the type-I muscle fibers a greater staining of ARs than within or near the type-II fibres. In conclusion, the protein ingestion hinders RE-induced increase in serum testosterone in older men but may not significantly affect muscle AR, MGF or IGF-IEa gene expression. Furthermore, the present study shows that even older men are able to increase muscle AR mRNA expression in response to a RE bout.     

Acute hormonal response to sublingual androstenediol intake in young men.

The effectiveness of orally ingested androstenediol in raising serum testosterone concentrations may be limited because of hepatic breakdown of the ingested androgens. Because androstenediol administered sublingually with cyclodextrin bypasses first-pass hepatic catabolism, we evaluated the acute hormonal response to sublingual cyclodextrin androstenediol supplement in young men. Eight men (22.9 +/- 1.2 yr) experienced in strength training consumed either 20 mg androstenediol in a sublingual cyclodextrin tablet (Sl Diol) or placebo (Pl) separated by at least 1 wk in a randomized, double-blind, crossover manner. Blood samples were collected before supplementation and at 30-min intervals for 3 h after supplementation. Serum hormone concentrations did not change with Pl. Serum androstenedione concentrations were increased (P < 0.05) above baseline (11.2 +/- 1.1 nmol/l) with Sl Diol from 60 to 180 min after intake and reached a peak concentration of 25.2 +/- 2.9 nmol/l at 120 min. Serum free testosterone concentrations were increased from 86.2 +/- 9.1 pmol/l with Sl Diol from 30 to 180 min and reached a peak concentration of 175.4 +/- 12.2 pmol/l at 60 min. Serum total testosterone concentrations increased above basal (25.6 +/- 2.3 nmol/l) from 30 to 180 min with Sl Diol and reached a peak concentration of 47.9 + 2.9 nmol/l at 60 min. Serum estradiol concentrations were elevated (P < 0.05) above baseline (0.08 +/- 0.01 nmol/l) from 30 to 180 min with Sl Diol and reached 0.14 +/- 0.02 nmol/l at 180 min. These data indicate that sublingual cyclodextrin androstenediol intake increases serum androstenedione, free testosterone, total testosterone, and estradiol concentrations.     

Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy

Administration of replacement doses of testosterone to healthy hypogonadal men and supraphysiological doses to eugonadal men increases muscle size. To determine whether testosterone-induced increase in muscle size is due to muscle fiber hypertrophy, 61 healthy men, 18-35 yr of age, received monthly injections of a long-acting gonadotropin-releasing hormone (GnRH) agonist to suppress endogenous testosterone secretion and weekly injections of 25, 50, 125, 300, or 600 mg testosterone enanthate (TE) for 20 wk. Thigh muscle volume was measured by magnetic resonance imaging (MRI) scan, and muscle biopsies were obtained from vastus lateralis muscle in 39 men before and after 20 wk of combined treatment with GnRH agonist and testosterone. Administration of GnRH agonist plus TE resulted in mean nadir testosterone concentrations of 234, 289, 695, 1,344, and 2,435 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively. Graded doses of testosterone administration were associated with testosterone dose and concentration-dependent increase in muscle volume measured by MRI (changes in vastus lateralis volume, -4, +7, +15, +32, and +48 ml at 25-, 50-, 125-, 300-, and 600-mg doses, respectively). Changes in cross-sectional areas of both type I and II fibers were dependent on testosterone dose and significantly correlated with total (r = 0.35, and 0.44, P < 0.0001 for type I and II fibers, respectively) and free (r = 0.34 and 0.35, P < 0.005) testosterone concentrations during treatment. The men receiving 300 and 600 mg of TE weekly experienced significant increases from baseline in areas of type I (baseline vs. 20 wk, 3,176 +/- 186 vs. 4,201 +/- 252 microm(2), P < 0.05 at 300-mg dose, and 3,347 +/- 253 vs. 4,984 +/- 374 microm(2), P = 0.006 at 600-mg dose) muscle fibers; the men in the 600-mg group also had significant increments in cross-sectional area of type II (4,060 +/- 401 vs. 5,526 +/- 544 microm(2), P = 0.03) fibers. The relative proportions of type I and type II fibers did not change significantly after treatment in any group. The myonuclear number per fiber increased significantly in men receiving the 300- and 600-mg doses of TE and was significantly correlated with testosterone concentration and muscle fiber cross-sectional area. In conclusion, the increases in muscle volume in healthy eugonadal men treated with graded doses of testosterone are associated with concentration-dependent increases in cross-sectional areas of both type I and type II muscle fibers and myonuclear number. We conclude that the testosterone induced increase in muscle volume is due to muscle fiber hypertrophy.     

Assessment of biomarkers of protein anabolism in skeletal muscle during the life span of the rat: sarcopenia despite elevated protein synthesis

Loss of muscle strength is a principal factor in the development of physical frailty, a condition clinically associated with increased risk of bone fractures, impairments in the activities of daily living, and loss of independence in older humans. A primary determinant in the decline in muscle strength that occurs during aging is a loss of muscle mass, which could occur through a reduction in the rate of protein synthesis, an elevation in protein degradation, or a combination of both. In the present study, rates of protein synthesis and the relative expression and function of various biomarkers involved in the initiation of mRNA translation in skeletal muscle were examined at different times throughout the life span of the rat. It was found that between 1 and 6 mo of age, body weight increased fourfold. However, by 6 mo, gastrocnemius protein synthesis and RNA content per gram of muscle were lower than values observed in 1-mo-old rats. Moreover, the relative expression of two proteins involved in the binding of initiator methionyl-tRNA to the 40S ribosomal subunit, eukaryotic initiation factors (eIF)2 and eIF2B, as well as the 70-kDa ribosomal protein S6 kinase, S6K1, was lower at 6 mo compared with 1 mo of age. Muscle mass, protein synthesis, and the aforementioned biomarkers remained unchanged until approximately 21 mo. Between 21 and 24 mo of age, muscle mass decreased precipitously. Surprisingly, during this period protein synthesis, relative RNA content, eIF2B activity, relative eIF2 expression, and S6K1 phosphorylation all increased. The results are consistent with a model wherein protein synthesis is enhanced during aging in a futile attempt to maintain muscle mass.     

Effects of an oral androgen on muscle and metabolism in older,community-dwelling men

To determine whether oxymetholone increases lean body mass (LBM) and skeletal muscle strength in older persons, 31 men 65-80 yr of age were randomized to placebo (group 1) or 50 mg (group 2) or 100 mg (group 3) daily for 12 wk. For the three groups, total LBM increased by 0.0 +/- 0.6, 3.3 +/- 1.2 (P < 0.001), and 4.2 +/- 2.4 kg (P < 0.001), respectively. Trunk fat decreased by 0.2 +/- 0.4, 1.7 +/- 1.0 (P = 0.018), and 2.2 +/- 0.9 kg (P = 0.005) in groups 1, 2, and 3, respectively. Relative increases in 1-repetition maximum (1-RM) strength for biaxial chest press of 8.2 +/- 9.2 and 13.9 +/- 8.1% in the two active treatment groups were significantly different from the change (-0.8 +/- 4.3%) for the placebo group (P < 0.03). For lat pull-down, 1-RM changed by -0.6 +/- 8.3, 8.8 +/- 15.1, and 18.4 +/- 21.0% for the groups, respectively (1-way ANOVA, P = 0.019). The pattern of changes among the groups for LBM and upper-body strength suggested that changes might be related to dose. Alanine aminotransferase increased by 72 +/- 67 U/l in group 3 (P < 0.001), and HDL-cholesterol decreased by -19 +/- 9 and -23 +/- 18 mg/dl in groups 2 and 3, respectively (P = 0.04 and P = 0.008). Thus oxymetholone improved LBM and maximal voluntary muscle strength and decreased fat mass in older men.     

Development of models to predict anabolic response to testosterone administration in healthy young men

Considerable heterogeneity exists in the anabolic response to androgen administration; however, the factors that contribute to variation in an individual's anabolic response to androgens remain unknown. We investigated whether testosterone dose and/or any combination of baseline variables, including concentrations of hormones, age, body composition, muscle function, and morphometry or polymorphisms in androgen receptor could explain the variability in anabolic response to testosterone. Fifty-four young men were treated with a long-acting gonadotropin-releasing hormone (GnRH) agonist and one of five doses (25, 50, 125, 300, or 600 mg/wk) of testosterone enanthate (TE) for 20 wk. Anabolic response was defined as a change in whole body fat-free mass (FFM) by dual-energy X-ray absorptiometry (DEXA), appendicular FFM (by DEXA), and thigh muscle volume (by magnetic resonance imaging) during TE treatment. We used univariate and multivariate analysis to identify the subset of baseline measures that best explained the variability in anabolic response to testosterone supplementation. The three-variable model of TE dose, age, and baseline prostate-specific antigen (PSA) level explained 67% of the variance in change in whole body FFM. Change in appendicular FFM was best explained (64% of the variance) by the linear combination of TE dose, baseline PSA, and leg press strength, whereas TE dose, log of the ratio of luteinizing hormone to testosterone concentration, and age explained 66% of the variation in change in thigh muscle volume. The models were further validated by using Ridge analysis and cross-validation in data subsets. Only the model using testosterone dose, age, and PSA was a consistent predictor of change in FFM in subset analyses. The length of CAG tract was only a weak predictor of change in thigh muscle volume and lean body mass. Hence, the anabolic response of healthy, young men to exogenous testosterone administration can largely be predicted by the testosterone dose.     

Muscle protein metabolism responds similarly to exogenous amino acids in healthy younger and older adults during NO-induced hyperemia

The combination of increasing blood flow and amino acid (AA) availability provides an anabolic stimulus to the skeletal muscle of healthy young adults by optimizing both AA delivery and utilization. However, aging is associated with a blunted response to anabolic stimuli and may involve impairments in endothelial function. We investigated whether age-related differences exist in the muscle protein anabolic response to AAs between younger (30 ± 2 yr) and older (67 ± 2 yr) adults when macrovascular and microvascular leg blood flow were similarly increased with the nitric oxide (NO) donor, sodium nitroprusside (SNP). Regardless of age, SNP+AA induced similar increases above baseline (P ≤ 0.05) in macrovascular flow (4.3 vs. 4.4 ml·min(-1)·100 ml leg(-1) measured using indocyanine green dye dilution), microvascular flow (1.4 vs. 0.8 video intensity/s measured using contrast-enhanced ultrasound), phenylalanine net balance (59 vs. 68 nmol·min(-1)·100 ml·leg(-1)), fractional synthetic rate (0.02 vs. 0.02%/h), and model-derived muscle protein synthesis (62 vs. 49 nmol·min(-1)·100 ml·leg(-1)) in both younger vs. older individuals, respectively. Provision of AAs during NO-induced local skeletal muscle hyperemia stimulates skeletal muscle protein metabolism in older adults to a similar extent as in younger adults. Our results suggest that the aging vasculature is responsive to exogenous NO and that there is no age-related difference per se in AA-induced anabolism under such hyperemic conditions.     

Short-term insulin and nutritional energy provision do not stimulate muscle protein synthesis if blood amino acid availability decreases

Muscle protein synthesis requires energy and amino acids to proceed and can be stimulated by insulin under certain circumstances. We hypothesized that short-term provision of insulin and nutritional energy would stimulate muscle protein synthesis in healthy subjects only if amino acid availability did not decrease. Using stable isotope techniques, we compared the effects on muscle phenylalanine kinetics across the leg of an amino acid-lowering, high-energy (HE, n = 6, 162 +/- 20 kcal/h) hyperglycemic hyperlipidemic hyperinsulinemic clamp with systemic insulin infusion to a low-energy (LE, n = 6, 35 +/- 3 kcal/h, P < 0.05 vs. HE) euglycemic hyperinsulinemic clamp with local insulin infusion in the femoral artery. Basal blood phenylalanine concentrations and phenylalanine net balance, muscle protein breakdown, and synthesis (nmol.min(-1).100 g leg muscle(-1)) were not different between groups. During insulin infusion, femoral insulinemia increased to a similar extent between groups and blood phenylalanine concentration decreased 27 +/- 3% in the HE group but only 9 +/- 2% in the LE group (P < 0.01 HE vs. LE). Phenylalanine net balance increased in both groups, but the change was greater (P < 0.05) in the LE group. Muscle protein breakdown decreased in the HE group (58 +/- 12 to 35 +/- 7 nmol.min(-1).100 g leg muscle(-1)) and did not change in the LE group. Muscle protein synthesis was unchanged in the HE group (39 +/- 6 to 30 +/- 7 nmol.min(-1).100 g leg muscle(-1)) and increased (P < 0.05) in the LE group (41 +/- 9 to 114 +/- 26 nmol.min(-1).100 g leg muscle(-1)). We conclude that amino acid availability is an important factor in the regulation of muscle protein synthesis in response to insulin, as decreased blood amino acid concentrations override the positive effect of insulin on muscle protein synthesis even if excess energy is provided.     

Ultrastructural muscle damage in young vs. older men after high-volume, heavy-resistance strength training.

This study assessed ultrastructural muscle damage in young (20-30 yr old) vs. older (65-75 yr old) men after heavy-resistance strength training (HRST). Seven young and eight older subjects completed 9 wk of unilateral leg extension HRST. Five sets of 5-20 repetitions were performed 3 days/wk with variable resistance designed to subject the muscle to near-maximal loads during every repetition. Biopsies were taken from the vastus lateralis of both legs, and muscle damage was quantified via electron microscopy. Training resulted in a 27% strength increase in both groups (P < 0.05). In biopsies before training in the trained leg and in all biopsies from untrained leg, 0-3% of muscle fibers exhibited muscle damage in both groups (P = not significant). After HRST, 7 and 6% of fibers in the trained leg exhibited damage in the young and older men, respectively (P < 0.05, no significant group differences). Myofibrillar damage was primarily focal, confined to one to two sarcomeres. Young and older men appear to exhibit similar levels of muscle damage at baseline and after chronic HRST.     

Treatment with oxandrolone and the durability of effects in older men.

We investigated the effects of the anabolic androgen, oxandrolone, on lean body mass (LBM), muscle size, fat, and maximum voluntary muscle strength, and we determined the durability of effects after treatment was stopped. Thirty-two healthy 60- to 87-yr-old men were randomized to receive 20 mg oxandrolone/day (n = 20) or placebo (n = 12) for 12 wk. Body composition [dual-energy X-ray absorptiometry (DEXA), magnetic resonance imaging, and (2)H(2)O dilution] and muscle strength [1 repetition maximum (1 RM)] were evaluated at baseline and after 12 wk of treatment; body composition (DEXA) and 1-RM strength were then assessed 12 wk after treatment was discontinued (week 24). At week 12, oxandrolone increased LBM by 3.0 +/- 1.5 kg (P < 0.001), total body water by 2.9 +/- 3.7 kg (P = 0.002), and proximal thigh muscle area by 12.4 +/- 8.4 cm(2) (P < 0.001); these increases were greater (P < 0.003) than in the placebo group. Oxandrolone increased 1-RM strength for leg press by 6.7 +/- 6.4% (P < 0.001), leg flexion by 7.0 +/- 7.8% (P < 0.001), chest press by 9.3 +/- 6.7% (P < 0.001), and latissimus pull-down exercises by 5.1 +/- 9.1% (P = 0.02); these increases were greater than placebo. Oxandrolone reduced total (-1.9 +/- 1.0 kg) and trunk fat (-1.3 +/- 0.6 kg; P < 0.001), and these decreases were greater (P < 0.001) than placebo. Twelve weeks after oxandrolone was discontinued (week 24), the increments in LBM and muscle strength were no longer different from baseline (P > 0.15). However, the decreases in total and trunk fat were sustained (-1.5 +/- 1.8, P = 0.001 and -1.0 +/- 1.1 kg, P < 0.001, respectively). Thus oxandrolone induced short-term improvements in LBM, muscle area, and strength, while reducing whole body and trunk adiposity. Anabolic improvements were lost 12 wk after discontinuing oxandrolone, whereas improvements in fat mass were largely sustained.     

Short vs. long rest period between the sets in hypertrophic resistance training: influence on muscle strength, size, and hormonal adaptations in trained men

Acute and long-term hormonal and neuromuscular adaptations to hypertrophic strength training were studied in 13 recreationally strength-trained men. The experimental design comprised a 6-month hypertrophic strength-training period including 2 separate 3-month training periods with the crossover design, a training protocol of short rest (SR, 2 minutes) as compared with long rest (LR, 5 minutes) between the sets. Basal hormonal concentrations of serum total testosterone (T), free testosterone (FT), and cortisol (C), maximal isometric strength of the leg extensors, right leg 1 repetition maximum (1RM), dietary analysis, and muscle cross-sectional area (CSA) of the quadriceps femoris by magnetic resonance imaging (MRI) were measured at months 0, 3, and 6. The 2 hypertrophic training protocols used in training for the leg extensors (leg presses and squats with 10RM sets) were also examined in the laboratory conditions at months 0, 3, and 6. The exercise protocols were similar with regard to the total volume of work (loads x sets x reps), but differed with regard to the intensity and the length of rest between the sets (higher intensity and longer rest of 5 minutes vs. somewhat lower intensity but shorter rest of 2 minutes). Before and immediately after the protocols, maximal isometric force and electromyographic (EMG) activity of the leg extensors were measured and blood samples were drawn for determination of serum T, FT, C, and growth hormone (GH) concentrations and blood lactate. Both protocols before the experimental training period (month 0) led to large acute increases (p < 0.05-0.001) in serum T, FT, C , and GH concentrations, as well as to large acute decreases (p < 0.05-0.001) in maximal isometric force and EMG activity. However, no significant differences were observed between the protocols. Significant increases of 7% in maximal isometric force, 16% in the right leg 1RM, and 4% in the muscle CSA of the quadriceps femoris were observed during the 6-month strength-training period. However, both 3-month training periods performed with either the longer or the shorter rest periods between the sets resulted in similar gains in muscle mass and strength. No statistically significant changes were observed in basal hormone concentrations or in the profiles of acute hormonal responses during the entire 6-month experimental training period. The present study indicated that, within typical hypertrophic strength-training protocols used in the present study, the length of the recovery times between the sets (2 vs. 5 minutes) did not have an influence on the magnitude of acute hormonal and neuromuscular responses or long-term training adaptations in muscle strength and mass in previously strength-trained men.     

Mixed muscle and hepatic derived plasma protein metabolism is differentially regulated in older and younger men following resistance exercise

We sought to determine whether exercise-induced muscle protein turnover alters the subsequent production of hepatically derived acute-phase plasma proteins, and whether age affects how these proteins are regulated. We measured arteriovenous (a-v) balance and the synthesis of mixed muscle protein, albumin (A) and fibrinogen (F) before exercise (REST) and from the beginning of exercise to 10, 60, and 180 min following a single bout of moderate-intensity leg extension exercise (POST-EX) in postabsorptive untrained older (n = 6) and younger (n = 6) men using L-[ring-2H5]phenylalanine (Phe). Subjects performed 6 sets of 8 repetitions of leg extension at 80% of their 1-RM (one-repetition maximum). All data are presented as the difference from REST (Delta from REST at 10, 60, and 180 min POST-EX). Mixed muscle fractional synthesis rate (FSR-M) increased significantly from the beginning of exercise until 10 min POST-EX in the older men (DeltaFSR-M: 0.044%/h), whereas FSR-M in the younger men was not elevated until 180 min POST-EX (DeltaFSR-M: 0.030%/h). FSR-A and FSR-F increased at all POST-EX periods in the older men (DeltaFSR-A = 10 min: 1.90%/day; 60 min: 2.72%/day; 180 min: 2.78%/day; DeltaFSR-F = 10 min: 1.00%/day; 60 min: 3.01%/day; 180 min: 3.73%/day). No change occurred in FSR-A in the younger men, but FSR-F was elevated from the beginning of exercise until 10 and 180 min POST-EX (10 min: 3.07%/day and 180 min: 3.96%/day). Net balance of Phe was positive in the older men in the immediate POST-EX period. Our data indicate that mixed muscle and hepatic derived protein synthesis is differentially regulated in younger and older men in response to a single bout of moderate-intensity leg extension exercise. Moreover, our data suggest that with age may come a greater need to salvage or make available amino acids from exercise-induced muscle protein breakdown to mount an acute-phase response.     

Changes in serum testosterone and estradiol concentrations following acute androstenedione ingestion in young women.

The effect of androstenedione intake on serum hormone concentrations in women is equivocal. Therefore, we examined the hormonal response to androstenedione intake in healthy young (22.1 +/- 0.4 y) women for 4 hours. On day 3 of the follicular phase, subjects ingested placebo, 100, or 300 mg androstenedione in a random, double-blind, cross-over manner. Blood samples were collected before and every 30 min for 240 min after intake. Serum androstenedione concentrations (means +/- SE) increased above basal (6.2 +/- 0.8 nmol/l) from 60-240 min for both 100 mg (22.6 +/- 1.0 nmol/l at 240 min) and 300 mg (28.1 +/- 1.3 nmol/l at 210 min). Androstenedione intake increased serum total testosterone concentrations above basal (1.2 +/- 0.2 nmol/l) from 120-240 min (5.5 +/- 0.9 nmol/l at 210 min) with 100 mg and from 60-240 with 300 mg (10.2 +/- 1.6 nmol/l at 210 min). Androstenedione intake also increased serum estradiol concentrations (basal 191 +/- 24 pmol/l) at 150 min with 100 mg (237 +/- 35 pmol/l) and from 150-240 min with 300 mg (reaching 260 +/- 32 pmol/l at 240 min). These data indicate that, in contrast to men, androstenedione intake in women increases serum testosterone concentrations.     

Effects of age on testosterone responses to resistance exercise and musculoskeletal variables in men

This study compared serum total testosterone (TT) and free testosterone (FT) responses of young (20-26 years, n = 8), middle-aged (38-53 years, n = 7), and older (59-72 years, n = 9) men to resistance exercise. We also examined the relationships between testosterone (T) levels and strength, bone mineral density (BMD), and body composition variables for each age group. Subjects were tested for isotonic muscular strength (1 repetition maximum [1RM]), BMD (dual-energy x-ray absorptiometry [DXA]) and body composition (DXA). Each group performed an acute exercise protocol (3 sets, 10 repetitions, 80% of 1RM, 6 exercises). Blood samples were obtained at baseline, immediately postexercise, and 15 minutes postexercise for the TT and FT assays. The older age group had significantly (p < 0.05) lower T levels than the young group, but each group exhibited an increase (p < 0.05) in TT and FT immediately postexercise. Total T and FT were significantly correlated (p < 0.05) with strength in middle-aged and older men and with bone-free lean tissue mass in older men. In conclusion, middle-aged and older men showed similar relative T responses to those of younger men to a single bout of high-intensity resistance exercise. However, T levels were related to strength and muscle mass only in middle-aged or older men. On a practical application level, older men can complete a high-intensity resistance exercise program resulting in spikes in T that may attenuate age-related muscle and BMD loss.     

Suppression of endogenous testosterone production attenuates the response to strength training: a randomized, placebo-controlled, and blinded intervention study

We hypothesized that suppression of endogenous testosterone would inhibit the adaptations to strength training in otherwise healthy men. Twenty-two young men with minor experience with strength training participated in this randomized, placebo-controlled, double-blinded intervention study. The subjects were randomized to treatment with the GnRH analog goserelin (3.6 mg) or placebo (saline) subcutaneously every 4 wk for 12 wk. The strength training period of 8 wk, starting at week 4, included exercises for all major muscles [3-4 sets per exercise x 6-10 repetitions with corresponding 6- to 10-repetition maximum (RM) loads, 3/wk]. A strength test, blood sampling, and whole body DEXA scan were performed at weeks 4 and 12. Endogenous testosterone decreased significantly (P < 0.01) in the goserelin group from 22.6 +/- 5.5 (mean +/- SD) nmol/l to 2.0 +/- 0.5 (week 4) and 1.1 +/- 0.6 nmol/l (week 12), whereas it remained constant in the placebo group. The goserelin group showed no changes in isometric knee extension strength after training, whereas the placebo group increased from 240.2 +/- 41.3 to 264.1 +/- 35.3 Nm (P < 0.05 within and P = 0.05 between groups). Lean mass of the legs increased 0.37 +/- 0.13 and 0.57 +/- 0.30 kg in the goserelin and placebo groups, respectively (P < 0.05 within and P = 0.05 between groups). Body fat mass increased 1.4 +/- 1.0 kg and decreased 0.6 +/- 1.2 kg in the goserelin and placebo groups, respectively (P < 0.05 within and between groups). We conclude that endogenous testosterone is of paramount importance to the adaptation to strength training.     

Effects of a short-term strength training programme on lymphocyte subsets at rest in elderly humans

The effects of a short-term strength training programme on resting lymphocyte subsets and stress hormone concentrations were analysed in 32 elderly sedentary subjects. Out of these 32 subjects, 8 women and 8 men [mean age 70.1 (SEM 1.0) years] were randomly assigned to a 8-week strength training programme which consisted of three sets of eight repetitions at 80% of one repetition maximum, for leg press, bilateral leg extension and seated chest press, 3 days a week. The remaining 8 women and 8 men [mean age 70.5 (SEM 0.9) years] served as controls. Absolute counts of lymphocyte subsets (CD20+, CD3+, CD3+CD4+, CD3+CD8+, CD3-CD56+CD16+) were measured with a new technique combining fluorescent microspheres and flow cytometry. In the trained subjects, substantial increases in strength took place in one repetition maximum during the 8-week training period for leg press [from means of 20.7 (SEM 1.0) to 23.6 (SEM 1.0) N x kg(-1) LBM (lean body mass)], chest press [from means of 5.4 (SEM 0.3) to 6.2 (SEM 0.3) N x kg(-1) LBM] and bilateral leg extension [from means of 6.3 (SEM 0.2) to 7.4 (SEM 0.3) N x kg(-1) LBM] movements. Baseline cortisol concentration (P < 0.01), CD20+ cell count (P < 0.05), CD3+ cell count (P < 0.05), and CD4+ cell count (P < 0.01) decreased in both groups secondary to circannual variations between winter and summer. No significant effect of strength training on resting adrenaline, noradrenaline and cortisol concentrations or distributions of lymphocyte subsets at rest was observed. The main finding of this study was to demonstrate that 8-week is too short a duration for a strength training programme to modify counts of lymphocyte subsets at rest in elderly sedentary adults.