Muscle mechano growth factor is preferentially induced by growth hormone in growth hormone-deficient lit/lit mice

Two muscle insulin-like growth factor-I (IGF-I) mRNA splice variants (IGF-IEa and IGF-IEb) have been identified in rodents. IGF-IEb, also called mechano growth factor (MGF) has been found to be upregulated by exercise or muscle damage. Growth hormone (GH) is the principal regulator of  IGF-I expression in several tissues including skeletal muscle. Therefore, we investigated the effect of chronic GH excess or disruption of GH receptor (GHR) signalling, and the acute effect of GH administration on expression of muscle IGF-I isoforms using transgenic mice that express bovine GH (bGH), GHR gene-disrupted (GHR–/–) mice and GH-deficient lit/lit mice before and after exogenous GH administration. MGF mRNA in skeletal muscle was increased in bGH mice whereas it was decreased in GHR–/– mice compared with control animals. Exogenous GH administration to dwarf lit/lit mice significantly increased muscle MGF but not IGF-IEa mRNA 4 h after treatment. Twelve hours after GH treatment, both MGF and IGF-IEa mRNAs in muscle were increased compared with vehicle-treated lit/lit mice. In contrast in GH-sufficient lit/+ mice, both MGF and IGF-IEa mRNAs were increased 4 h after and returned to the basal level 12 h after GH treatment. Hepatic IGF-I isoforms were regulated in parallel by GH. Thus, our results demonstrated that: (1) MGF mRNA in skeletal muscle is expressed in parallel with GH action; (2) MGF mRNA in muscle is produced preferentially in the situation of GH deficiency in contrast to the pattern in the GH-sufficient state; and (3) the induction of IGF-I isoforms by GH is tissue-specific.     

Muscle satellite (stem) cell activation during local tissue injury and repair

In post-mitotic tissues, damaged cells are not replaced by new cells and hence effective local tissue repair mechanisms are required. In skeletal muscle, which is a syncytium, additional nuclei are obtained from muscle satellite (stem) cells that multiply and then fuse with the damaged fibres. Although insulin-like growth factor-I (IGF-l) had been previously implicated, it is now clear that muscle expresses at least two splice variants of the IGF-I gene: a mechanosensitive, autocrine, growth factor (MGF) and one that is similar to the liver type (IGF-IEa). To investigate this activation mechanism, local damage was induced by stretch combined with electrical stimulation or injection of bupivacaine in the rat anterior tibialis muscle and the time course of regeneration followed morphologically. Satellite cell activation was studied by the distribution and levels of expression of M-cadherin (M-cad) and related to the expression of the two forms of IGF-I. It was found that the following local damage MGF expression preceded that of M-cad whereas IGF-IEa peaked later than M-cad. The evidence suggests therefore that an initial pulse of MGF expression following damage is what activates the satellite cells and that this is followed by the later expression of IGF-IEa to maintain protein synthesis to complete the repair.     

Gene expression in muscle in response to exercise

Muscle has an intrinsic ability to adapt to different types of work by changing fibre type and muscle mass. This process involves quantitative and qualitative changes in gene expression including those of the myosin heavy chain (MyHC) isogenes that encode different types of molecular motors. Increased expression of slow MyHC and of metabolic genes result in increased fatigue resistance. Recently, there has been some insight into how oxidative metabolism, as well as slow myosin expression, is regulated and the role of calcium in initiating switches in gene expression. In relation to muscle mass and power output it has been appreciated that local as well as systemic factors are important. Our group have cloned three types of IGF-I in human muscle which are derived from the IGF-I gene by alternative splicing. The expression of one of these that appears to be an autocrine/paracrine splice variant is only detectable after mechanical stimulation (MGF) and a systemic type (IGF-IEa) that is produced by the liver and other tissue including muscle. As the result of a reading frame shift, the MGF peptide has a different C terminal sequence to IGF-IEa. Interestingly, the MGF C terminal peptide has been found to act as a separate growth factor and to initially activate mononluceated myoblasts (satellite cells). MGF also responds to different signals and has different expression kinetics to IGF-IEa. The mechanotransduction mechanism for this signalling may directly or indirectly involve the dystrophin complex as dystrophic muscle, unlike normal muscle, is unable to express MGF in response to overload. Also the ability to express MGF has been found to decline markedly during ageing. The deficiency in expressing MGF and activating satellite cells in dystrophic and aged muscles may explain why muscle mass is not maintained in these situations. However, in normal muscle MGF appears to initiate local muscle repair with its over expression resulting in hypertrophy. This revised version was published online in August 2006 with corrections to the Cover Date.     

No effect of growth hormone administration on substrate oxidation during exercise in young, lean men

The purpose of this study was to examine the effects of increased fat availability induced by growth hormone (GH) administration on the oxidative metabolism during exercise. Seven well-trained males (age 25 ± 2 years (mean ± s.e.m. ); peak oxygen consumption     : 62 ± 1 ml min⁻¹ kg⁻¹ (completed four randomised trials: 120 min bicycling at 55%     4 h after receiving either 7.5 IU (2.5 mg) GH or placebo (Plc), and during rest after receiving either GH or Plc. In all studies a standardized meal was given 2 h after GH or Plc injection. GH administration resulted in an ∼60-fold increase in serum GH concentration at rest ( P < 0.0001) and during exercise ( P < 0.0001). The increase in serum GH was followed by an increase in circulating glycerol at rest (8%, P < 0.0001). When combined with exercise the increase in plasma glycerol was more pronounced (GH: 716% of baseline versus Plc: 328%, P < 0.0001). However, this increase in fat mobilization did not increase fat oxidation during exercise (indirect calorimetry). In conclusion, GH administration combined with aerobic exercise increased lipolytic parameters substantially more than exercise alone, but did not further augment whole body fat oxidation.     

Expression of specific IGFBPs is associated with those of the proliferating and differentiating markers in regenerating rat plantaris muscle

To examine the relationship between specific insulin-like growth factor (IGF)-binding proteins (IGFBPs) and myogenesis during muscle regeneration in vivo, we measured mRNA expression of IGFBPs and myogenic markers in rat plantaris muscle after bupivacaine administration. IGF-I Ea, MGF, IGFBPs and myogenic marker mRNAs were analyzed 12, 24, 48 and 72 h after bupivacaine injection. IGFBP-1, -2, -3 and -4 proteins were immunostained after the treatment. MGF, IGF-I Ea and IGFBP-4 mRNAs started to increase 12 or 24 h after bupivacaine injection and increased further after that. IGFBP-1, -2, -3 and -4 proteins were strongly stained in the immature muscle fiber nuclei and the extracellular matrix after bupivacaine injection. PCNA, MyoD, IGFBP-2 and IGFBP-3 mRNAs increased at 12 or 24 h and did not show further increases after that. Myogenin, p21, IGFBP-1 and IGFBP-5 mRNAs sharply increased after 72 h. These results suggest that specific IGFBPs are individually expressed and differently associated with the expression of myogenic markers in regenerating muscles.     

Local changes of IGF-I mRNA,GH receptor mRNA,and fiber size in rat plantaris muscle following compensatory overload

We investigated whether local insulin-like growth factor-I (IGF-I) mRNA and growth hormone (GH) receptor mRNA expressions in plantaris muscle were related to the region-specific hypertrophy following compensatory overload. Adult male normal or hypophysectomized rats were subjected to unilateral distal-half removals of the gastrocnemius and soleus muscles. The contralateral hindlimb was used as the control. Two weeks later, fiber areas in the distal and proximal parts of the plantaris muscle were measured. All the fiber areas measured in the distal part of the plantaris muscle in normal and hypophysectomized rats were significantly increased following the compensatory overload. In the proximal part, fiber areas of type I, IIA, and IIC were significantly increased, but fiber area of type IIB did not change. IGF-I mRNA expressions in the distal and proximal parts were increased 3 d after the compensatory overload in normal and hypophysectomized rats. The increase of IGF-I mRNA expression in the distal part 3 d after compensatory overload was greater than those in the proximal part. IGF-I mRNA expressions in the distal and proximal parts were increased 14 d after the compensatory overload in hypophysectomized rats, but not in normal rats. GH receptor mRNA expressions were decreased following compensatory overload, and almost disappeared 14 d after the compensatory overload in hypophysectomized rats. Thus muscle fiber hypertrophy following compensatory overload was different among the parts in a muscle and IGF-I mRNA was expressed in concert with the region-specific hypertrophy, but not GH receptor mRNA.     

Melatonin increases serum growth hormone and insulin-like growth factor I (IGF-I) levels in male Syrian hamsters via hypothalamic neurotransmitters.

In male Syrian hamsters daily evening melatonin injections resulted in increased circulating levels of growth hormone (GH), as well as a modest increase in body weight. A substantial increase in serum levels of insulin-like growth factor I (IGF-I) was observed in all hamsters receiving evening injections of melatonin for 10 weeks. The melatonin-induced increase in serum IGF-I levels was interpreted as a result of increased release of GH during the 10 week period of melatonin administration. The increase in serum GH and IGF-I was associated with significantly decreased hypothalamic turnover of norepinephrine (NE). Since blocking NE synthesis with alpha methyl-p-tyrosine reduced serum GH, the melatonin-induced increase in GH could not readily be attributed to decreased NE turnover. Highly significant increases in 5-hydroxyindole acetic acid (5HIAA) concentrations and in ratios of 5HIAA to serotonin (5HT) were noted in extracts of hypothalamus and in extracts of brain stem, suggesting a serotonergic component to melatonin-induced increase in GH-induced IGF secretion and subsequent growth.     

Growth hormone stimulates the collagen synthesis in human tendon and skeletal muscle without affecting myofibrillar protein synthesis

In skeletal muscle and tendon the extracellular matrix confers important tensile properties and is crucially important for tissue regeneration after injury. Musculoskeletal tissue adaptation is influenced by mechanical loading, which modulates the availability of growth factors, including growth hormone (GH) and insulin-like growth factor-I (IGF-I), which may be of key importance. To test the hypothesis that GH promotes matrix collagen synthesis in musculotendinous tissue, we investigated the effects of 14 day administration of 33–50 μg kg⁻¹ day⁻¹ recombinant human GH (rhGH) in healthy young individuals. rhGH administration caused an increase in serum GH, serum IGF-I, and IGF-I mRNA expression in tendon and muscle. Tendon collagen I mRNA expression and tendon collagen protein synthesis increased by 3.9-fold and 1.3-fold, respectively ( P < 0.01 and P = 0.02), and muscle collagen I mRNA expression and muscle collagen protein synthesis increased by 2.3-fold and 5.8-fold, respectively ( P < 0.01 and P = 0.06). Myofibrillar protein synthesis was unaffected by elevation of GH and IGF-I. Moderate exercise did not enhance the effects of GH manipulation. Thus, increased GH availability stimulates matrix collagen synthesis in skeletal muscle and tendon, but without any effect upon myofibrillar protein synthesis. The results suggest that GH is more important in strengthening the matrix tissue than for muscle cell hypertrophy in adult human musculotendinous tissue.     

Growth hormone does not increase the expression of insulin-like growth factors and their receptor genes in the pre-menopausal human ovary

A growing body of information now supports the existence of a complete intraovarian insulin-like growth factor I (IGF-I) system. Although the precise role of IGF-I in the context of ovarian physiology remains to be determined, it is likely that IGF-I may engage in the amplification of gonadotrophin hormonal action. These facts and experiments with animals establishing the ovaries of multiple species as a site of growth hormone (GH) reception and action have led to the use of recombinant GH (rGH) as an adjunctive agent to potentiate ovulation induction by exogenous gonadotrophins. Whether intraovarian IGF-I plays an intermediary role in GH hormonal action at the ovarian level remains uncertain at present. The aim of this study was to evaluate whether rGH administration to pre-menopausal women could modify the expression of the IGF-I gene in the ovary. The expression of the IGF-I gene was examined in a time-dependent manner in normal pre-menopausal ovaries obtained from nine women treated with rGH and nine control women treated with placebo, using solution hybridization/RNase protection assays. Ovarian tissue samples were obtained 24 h (six women) and 7 days (12 women) following rGH/placebo injection. Total RNA (20 microg) from whole pre-menopausal ovaries (with or without rGH treatment) as well as from human granulosa cells was hybridized with a human IGF-I antisense RNA. IGF-I peptide, but not oestradiol, serum concentrations increased significantly 24 h after rGH injection. IGF-I gene, however, was not expressed in the luteinized granulosa cells and whole pre-menopausal ovaries irrespectively of rGH treatment in ovarian samples analysed both 1 and 7 days following rGH injection. On the contrary, IGF-II mRNA transcribed from the fetal or fetal-neonatal IGF-II promoter and IGF-I receptor mRNA (both used as hybridization control) were both found in whole pre-menopausal ovary and luteinized granulosa cells. Nevertheless, no changes in the hybridization patterns were seen in the absence or presence of rGH. These studies demonstrate that rGH administration to normal premenopausal women does not change the expression of insulin-like growth factors and their receptor genes in the pre-menopausal human ovary. Furthermore, these results provide further evidence against locally produced IGF-I as responsible for any ovarian effects seen in systemic rGH administration.     

Somatotroph response to periodical IGF-I administration to male rats

Insulin-like growth factor I (IGF-I) downregulates growth hormone (GH) expression in pituitary cell cultures. However, in vivo different results were found depending on the experimental protocol used. We determined the kinetics of changes of pituitary and serum GH concentrations after subcutaneous IGF-I administration (240µg/100 g body weight) to rats every 12h for various periods. These parameters were correlated with changes in the somatotroph cell population. A significant increase in serum GH was registered at 6h after IGF-I injection. At this time, some somatotroph cells exhibited ultrastructurally signs of high secretory activity, whereas adjacent somatotroph cells showed a quiescent appearance with sizeable stores of secretory granules. In contrast, serum GH levels remained unchanged at 1, 2 and 12h after each IGF-I injection. Pituitary GH concentrations were comparable to control levels during the first 48h and declined significantly at 72h and 96h of IGF-I treatment. After these prolonged periods of time of treatment, the size and extension of organelles involved in protein synthesis decreased and mature secretory granules in the cytoplasm increased significantly in GH-secreting cells. The somatotroph cell density remained unchanged even at 96h of treatment. In conclusion, our results suggest that periodical IGF-I administration to rats does not inhibit GH secretion. Interestingly, IGF-I injections induced early and significant increases in serum GH levels. This result may be a consequence of a temporary stimulatory action on somatotroph cells concurrent with increased secretory activity.Key words:     

Growth hormone and IGF-I stimulate cell function in distinct zones of the rat epiphyseal growth plate

Proliferation and maturation of growth plate chondrocytes are primarily responsible for linear bone elongation, although the exact mechanisms involved have not been fully characterized. We have used discrete chondrocyte populations to address the mode of growth hormone (GH) action on the growth plate. Low doses of GH, and insulin-like growth factor-I (IGF-I) preferentially enhanced cell proliferation in proliferative zone chondrocytes; the mitogenic response of immature proliferative and resting zone cells was minimal. Proliferation was not enhanced by combining the effects of GH and IGF-I. Exposure to IGF-I increased IGF-I mRNA in resting zone cells. Both GH and IGF-I stimulated the accumulation of IGF-I receptor mRNA in the most immature proliferative zone cells but did not alter the accumulation of IGF-binding protein 4 mRNA in any fraction. These results confirm a direct effect of GH on growth plate chondrocytes and suggest that GH preferentially acts on the actively proliferating chondrocytes.     

Insulin-like growth factor system in patients with HIV infection: effect of exogenous growth hormone administration.

The purpose of this study was to characterize changes in the levels of insulin-like growth factor-I (IGF-I) and IGF binding proteins (BP) 1, 2, and 3 in HIV-infected adults throughout the course of their disease, and to assess the responsiveness of the IGF system components to growth hormone (GH) administration (6 mg/day) for 2 weeks. Healthy control study subjects (n = 10) were compared with patients who were either HIV-positive (n = 9), had AIDS without weight loss (n = 13), or had AIDS with >10% weight loss (n = 6), all of whom had been free of acute illness for at least 3 months. Under basal conditions, fasting serum concentrations of epinephrine, norepinephrine, cortisol, glucagon, insulin, IGF-I, and IGFBP-3 were not significantly different among the four groups. The serum concentrations of IGFBP-1 and IGFBP-2 were significantly higher in AIDS patients with wasting than in the other three groups (p < .05). In addition, there was a statistically significant positive correlation between the levels of IGFBP- 1 (p = .004) and IGFBP-2 (p = .03) and the stage of disease. Following GH administration, the serum concentrations of insulin and IGF-I were increased in all groups (p < .05). In addition, the increases in insulin levels correlated with stage of disease (p = .004). The responses of the IGFBPs were more variable. GH administration significantly increased the levels of IGFBP-3 in all groups except the patients with AIDS wasting, whereas the levels of IGFBP-1 were significantly decreased in controls and AIDS patients. These results demonstrate that there is a continuum of both elevations in the IGFBPs and altered metabolic responsiveness in patients infected with HIV that increases with the severity of the disease. These data also demonstrate that AIDS patients, who are free from secondary infection, respond to administration of GH by significantly increasing hepatic IGF-I production.     

Glomerular lesions in mice transgenic for growth hormone and insulinlike growth factor-I. I. Relationship between increased glomerular size and mesangial sclerosis.

The glomeruli of mice transgenic for bovine growth hormone (GH mice) were disproportionately enlarged as a function of either kidney or body weight. Glomerular size correlated with mesangial sclerosis and the urine albumin/creatinine ratio. The glomerular lesions consisted of mesangial proliferation (4 to 5 weeks) followed by progressive mesangial sclerosis (19 weeks), resulting in complete glomerulosclerosis at 30 to 37 weeks. Albuminuria paralleled the glomerulosclerosis. In contrast, mice transgenic for insulinlike growth factor-I (IGF-I mice) did not develop glomerulosclerosis, even though glomerular size significantly increased. Glomerular hypertrophy, however, did not reach that in GH mice. These data suggest that high levels of circulating GH lead to a disproportionate increase in glomerular cellularity and volume, as well as glomerulosclerosis. This does not appear to be the result of high levels of circulating IGF-I stimulated by GH, as the serum IGF-I level in GH mice was lower than that in IGF-I mice.     

Mecasermin

Mecasermin (recombinant human insulin-like growth factor-I [IGF-I]) is approved in the US for the long-term treatment of growth failure in children with severe primary IGF-I deficiency or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH, and in the EU for the long-term treatment of growth failure in children and adolescents with severe primary IGF-I deficiency. Subcutaneous mecasermin 0.12 mg/kg twice daily stimulated linear growth in children with growth failure and severe IGF-I deficiency associated with GH insensitivity, according to the results of a noncomparative, multicenter trial (n = 76) [mean duration of therapy 4.4 years; range 0.04-12.5 years]. During the first year of treatment, height velocity significantly increased from a mean 2.8 cm/year at baseline to a mean 8.0 cm/year; mean growth velocities remained above baseline for up to 8 years. Mecasermin also promoted statural growth in a small noncomparative trial in children with growth failure and GH insensitivity syndrome (n = 8). After 6.5-7.5 years of mecasermin therapy, the mean increase in the height standard deviation score was +1.4. Mecasermin was also shown to have beneficial effects in various other conditions including diabetes mellitus and anorexia nervosa. Subcutaneous mecasermin was generally well tolerated in children with severe IGF-I deficiency associated with GH insensitivity.     

Overload training inhibits phagocytosis and ROS generation of peritoneal macrophages: role of IGF-1 and MGF

We tested the hypothesis that overload training inhibits the phagocytosis and the reactive oxygen species (ROS) generation of peritoneal macrophages (M?s), and that insulin-like growth factor-1(IGF-1) and mechano-growth factor (MGF) produced by macrophages may contribute to this process. Rats were randomized to two groups, sedentary control group (n = 10) and overload training group (n = 10). The rats of overload training group were subjected to 11 weeks of experimental training protocol. Blood sample was used to determine the content of hemoglobin, testosterone, and corticosterone. The phagocytosis and the ROS generation of M?s were measured by the uptake of neutral red and the flow cytometry, respectively. IGF-1 and MGF mRNA levels in M?s were determined by real-time PCR. In addition, we evaluated the effects of IGF-1 and MGF peptide on phagocytosis and ROS generation of M?s in vitro. The data showed that overload training significantly decreased the body weight (19.3 %, P < 0.01), the hemoglobin (13.5 %, P < 0.01), the testosterone (55.3 %, P < 0.01) and the corticosterone (40.6 %, P < 0.01) in blood. Moreover, overload training significantly decreased the phagocytosis (27 %, P < 0.05) and the ROS generation (35 %, P < 0.01) of M?s. IGF-1 and MGF mRNA levels in M?s from overload training group increased significantly compared with the control group (21-fold and 92-fold, respectively; P < 0.01). In vitro experiments showed that IGF-1 had no significant effect on the phagocytosis and the ROS generation of M?s. Unlike IGF-1, MGF peptide impaired the phagocytosis of M?s in dose-independent manner. In addition, MGF peptide of some concentrations (i.e., 1, 10, 50, 100 ng/ml) significantly inhibited the ROS generation of M?s. These results suggest that overload training inhibits the phagocytosis and the ROS generation of peritoneal macrophages, and that MGF produced by macrophages may play a key role in this process. This may represent a novel mechanism of immune suppression induced by overload training.     

Effects of pulsatile cortisol infusion on sleep-EEG and nocturnal growth hormone release in healthy men

SUMMARY  This study investigates the short-term effects of pulsatile cortisol administrations upon sleep electroencephalogram (EEG) and spontaneous release of growth hormone (GH) in humans. Ten young healthy male volunteers received intravenous injections of either placebo or cortisol every 60 min between 17.00 hours and 06.00 hours (1 mg kg^-1 BW with a loading dose of 20% starting at 17.00 hours, followed by a dose of 6% every hour until 06.00 hours). The amount of rapid eye-movement (REM) sleep was significantly reduced (placebo: 19.9 ± 1.8; cortisol: 12.2 ± 1.5%; P < 0.05), whereas the time spent in slow-wave sleep (SWS) was significantly increased (placebo: 9.4 ± 1.6; cortisol: 13.9 ± 1.9%; P < 0.05). The SWS-promoting effect was most prominent during the first hours of sleep, but tended to persist also during the second half of the night. The pulsatile cortisol administration augmented the total amount of plasma GH concentrations (mean area under the time course curve, AUC, placebo: 3.2 ± 0.5; cortisol: 4.4 ± 0.6 [ng × 1000 × ml min^-1]; P < 0.05) due to an increase of GH release before sleep onset, and during the second half of the night, while the GH surge at sleep onset remained unchanged.
Our data are in accordance with the hypotheses that cortisol-induced changes of both sleep-EEG and GH secretion involve a common mechanism that includes activation of the hypothalamic-somatotrophic (growth hormone releasing hormone-growth hormone) system.     

Supplemental growth hormone alters body composition, muscle protein metabolism and serum lipids in fit adults: characterization of dose-dependent and response-recovery effects

Using double-blind, placebo-controlled procedures, the effects of low and high therapeutic dosages of methionyl-human growth hormone (met-hGH) on body composition, muscle protein metabolism and serum lipids were studied in 7 fit adults without growth hormone (GH) deficiency. Dose-dependent changes in body composition were observed that in part appeared to be influenced by a response-recovery effect, as measured by responses factored according to the duration of washout between exposure to the low and high dosages of met-hGH (6 weeks vs. 12 weeks vs. 18 weeks). Increases in fat-free weight were accompanied by an increase in skeletal muscle protein metabolism. Basal levels of cholesterol were inversely related to peak levels of GH in response to exercise stimulation and IGF-I, while GH supplementation lowered levels of total cholesterol and high- and low-density lipoproteins. A dose-dependent effect occurred for total cholesterol, and the percent change in cholesterol was related to the percent change in insulin-like growth factor I (IGF-I). Endogenous levels of GH were attenuated in response to stimulation and IGF-I levels were increased after treatment with GH, but no dose-dependent changes were observed. We conclude that met-hGH alters body composition and muscle protein metabolism, and decreases stored and circulating lipids in fit adults with a pre-existing supranormal body composition. The physiological profile of the person was not as important as the treatment conditions in determining the somatic and physiological response outcomes.     

Gene expression in distinct regions of rat tendons in response to jump training combined with anabolic androgenic steroid administration

The aim of this study was to evaluate the expression of key genes responsible for tendon remodeling of the proximal and distal regions of calcaneal tendon (CT), intermediate and distal region of superficial flexor tendon (SFT) and proximal, intermediate and distal region of deep flexor tendon (DFT) submitted to 7 weeks of jumping water load exercise in combination with AAS administration. Wistar male rats were grouped as follows: sedentary (S), trained (jumping water load exercise) (T), sedentary animals treated with AAS (5 mg/kg, twice a week) and animals treated with AAS and trained (AAST). mRNA levels of COL1A1, COL3A1, TIMP-1, TIMP-2, MMP-2, IGF-IEa, GAPDH, CTGF and TGF-β-1 were evaluated by quantitative PCR. Our main results indicated that mRNA levels alter in different regions in each tendon of sedentary animals. The training did not alter the expression of COL1A1, COL3A, IGF-IEa and MMP-2 genes, while AAS administration or its combination with training reduced their expression. This study indicated that exercise did not alter the expression of collagen and related growth factors in different regions of rat tendon. Moreover, the pattern of gene expression was distinct in the different tendon regions of sedentary animals. Although, the RNA yield levels of CT, SFT and DFT were not distinct in each region, these regions possess not only the structural and biochemical difference, but also divergence in the expression of key genes involved in tendon adaptation.