Effects of transdermal estrogen on collagen turnover at rest and in response to exercise in postmenopausal women

2012 ◽  
Vol 113 (7) ◽  
pp. 1040-1047 ◽  
Author(s):  
J. Pingel ◽  
H. Langberg ◽  
D. Skovgård ◽  
S. Koskinen ◽  
A. Flyvbjerg ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Postmenopausal Women ◽  
Acute Exercise ◽  
Type I Collagen ◽  
Control Period ◽  
Vastus Lateralis Muscle ◽  
Type I ◽  
Relative Role ◽  
Igf I ◽  
Transdermal Estrogen

Menopause is associated with loss of collagen content in the skin and tendon as well as accumulation of noncontractile tissue in skeletal muscle. The relative role of hormones and physical activity on these changes is not known. Accordingly, in a randomized, controlled, crossover study we investigated effects of transdermal estrogen replacement therapy (ERT) on type I collagen synthesis in tendon and skeletal muscle in 11 postmenopausal women. Patches with estrogen (Evorel) were placed on the skin above the patellar tendons and compared with no patch (control period). On day 2 all subjects performed one-legged exercise, and thereafter the exercised leg (EX leg) was compared with the nonexercised leg (Rest leg). Microdialysis catheters were placed in front of the patellar tendons and in the vastus lateralis muscle of both legs at days 3 and 5. The collected dialysate was analyzed for procollagen type I NH2-terminal propeptide (PINP), insulin-like growth factor I (IGF-I), and interleukin-6 (IL-6). Neither loading (Rest leg vs. EX leg) nor treatment (control vs. ERT) influenced peritendinous PINP, whereas combined exercise and ERT enhanced muscle PINP after 72 h (interaction between loading and treatment P = 0.008). In neither skeletal muscle nor peritendinous fluid were IGF-I and IL-6 influenced by treatment or exercise. In conclusion, ERT was associated with enhanced synthesis of type I collagen in the skeletal muscle in response to acute exercise. In perspective, this indicates that the availability of estrogen in postmenopausal women is important for repair of muscle damage or remodeling of the connective tissue within the skeletal muscle after exercise.

scholarly journals Effects of Intranasal 17β-Estradiol on Bone Turnover and Serum Insulin-Like Growth Factor I in Postmenopausal Women

1999 ◽  
Vol 84 (7) ◽  
pp. 2390-2397
Author(s):  
Patrick Garnero ◽  
Yannis Tsouderos ◽  
Istvan Marton ◽  
Clara Pelissier ◽  
Claire Varin ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Turnover ◽  
Postmenopausal Women ◽  
Type I Collagen ◽  
Serum Insulin ◽  
Type I ◽  
Factor I ◽  
Igf I ◽  
17Β Estradiol ◽  
Igfbp 3

Estrogen therapy, using either oral or transdermal routes, decreases bone turnover and prevents postmenopausal bone loss. It has been suggested that oral and transdermal 17β-estradiol (E2) may have different effects on serum insulin-like growth factor I (IGF-I), a potent bone-forming growth factor. In this study we investigated the effects of a new route of administration, the intranasal E2 spray (S21400), on bone turnover and circulating IGF-I and IGF-binding protein-3 (IGFBP-3). Four hundred and twenty early postmenopausal women (<5 yr since menopause; mean age, 52 yr) were enrolled in a 3-month, double blind, placebo-controlled study of four doses of intranasal E2 (100, 200, 300, and 400μ g/day), two doses of oral E2 valerate (1 or 2 mg/day), and placebo. One hundred and twelve women were further treated for 12 months with intranasal E2 (300 μg/day, i.e. the dose that has been shown to be adequate for the majority of postmenopausal women). Markers of bone resorption (urinary type I collagen C telopeptides) and formation [serum osteocalcin, serum type I collagen N-terminal extension propeptide (PINP), and serum bone alkaline phosphatase (BAP)] were measured at baseline, 1 month, 3 months, and 15 months. Serum IGF-I and IGFBP-3 were measured at baseline, 1 month, and 3 months. Urinary type I collagen C telopeptides decreased significantly in all active treatment groups as soon as 1 month (P < 0.001 vs. placebo) and continued to decrease at 3 months with a dose effect for intranasal E2. Serum osteocalcin and PINP did not change at 1 month for oral E2 (1 and 2 mg), but decreased significantly at 3 months. In contrast, formation markers increased significantly at 1 month for the two highest doses of intranasal E2 (P < 0.01 vs. placebo for osteocalcin and BAP) and did not decrease at 3 months. Oral E2 induced a marked decrease in circulating IGF-I as early as 1 month, which was amplified at 3 months (−29% and −32% for 1 and 2 mg, respectively), whereas no significant change from placebo was observed for intranasal E2 during the 3-month period. Changes in circulating IGF-I correlated significantly (P < 0.01) with changes in osteocalcin, PINP, and BAP at 3 months. Oral and intranasal E2 did not induce any significant change from placebo in serum IGFBP-3 at both 1 and 3 months. After 1 yr of treatment with intranasal E2 (300μ g/day), both resorption and formation markers decreased, reaching the levels in premenopausal women, regardless of the type of treatment during the first 3 months. We conclude that E2 administered by this new nasal route normalizes bone turnover to premenopausal levels. The delayed decrease in bone formation observed with intranasal E2 compared to oral E2 may be related to different effects on serum IGF-I levels.

Exercise-dependent IGF-I, IGFBPs, and type I collagen changes in human peritendinous connective tissue determined by microdialysis

2007 ◽  
Vol 102 (1) ◽  
pp. 214-220 ◽  
Author(s):  
Jens L. Olesen ◽  
Katja M. Heinemeier ◽  
Carsten Gemmer ◽  
Michael Kjær ◽  
Allan Flyvbjerg ◽  
...  
Keyword(s):  
Mechanical Loading ◽  
Collagen Synthesis ◽  
Acute Exercise ◽  
Type I Collagen ◽  
Exercise Group ◽  
Control Group ◽  
Local Concentration ◽  
Type I ◽  
Collagen Production ◽  
Igf I

Microdialysis studies indicate that mechanical loading of human tendon during exercise elevates type I collagen production in tendon. However, the possibility that the insertion of microdialysis fibers per se may increase the local collagen production due to trauma has not been explored. Insulin-like growth factor I (IGF-I) and its binding proteins (IGFBPs), which are known to stimulate collagen production in animal tendons, may regulate the translation of mechanical loading to collagen synthesis. Systemic and tissue levels of IGF-I, IGFBP, and type I collagen metabolism markers [procollagen I COOH-terminal propeptide (PICP) and COOH-terminal telopeptide of type I collagen] were measured by microdialysis in peritendinous tissue of the human Achilles tendon in an exercise group (performing a 36-km run, n = 6) and a control group (no intervention, n = 6). An increase in local PICP concentration was seen in both groups after 72 h and stayed elevated in the exercise group at 96 h ( P < 0.05). IGFBP-1 in both serum and dialysate increased in the exercise group immediately after exercise ( P < 0.05), whereas IGFBP-3 decreased systemically ( P < 0.05). Elevation of local IGFBP-4 was observed in both the control and exercise groups after 48 h ( P < 0.05). Total IGF-I did not change in locally or systemically in either group. Our results indicate an increased local production of PICP in human peritendinous tissue in response to prolonged mechanical loading with part of the increase due to trauma from the sampling technique. Care must therefore be emphasized to minimize the numbers of insertions with microdialysis. We demonstrated an elevation of IGFBP-1 both systemically and peritendinously in response to prolonged acute exercise. The local increased collagen synthesis was preceded by an elevation of local concentration of IGFBP-4, suggesting that IGFBP-4 may have a key role in the IGF-axis effect on the human collagen synthesis in vivo.

scholarly journals Responses of Markers of Bone and Collagen Turnover to Exercise, Growth Hormone (GH) Administration, and GH Withdrawal in Trained Adult Males1

2000 ◽  
Vol 85 (1) ◽  
pp. 124-133 ◽  
Author(s):  
Jennifer D. Wallace ◽  
Ross C. Cuneo ◽  
Per Arne Lundberg ◽  
Thord Rosén ◽  
Jens Otto Lunde Jørgensen ◽  
...  
Keyword(s):  
Acute Exercise ◽  
Type I Collagen ◽  
Controlled Study ◽  
Bone Resorption Marker ◽  
Type I ◽  
Serum Osteocalcin ◽  
Collagen Turnover ◽  
Gh Treatment ◽  
Type I Procollagen ◽  
Procollagen Iii

To examine the interactions between acute exercise and GH on markers of bone and collagen turnover and to assess the potential for detecting GH abuse in athletes using these markers, we studied 17 aerobically trained males (age, 26.9 ± 1.5 yr). Sequential studies of exercise, GH administration, and GH withdrawal were undertaken. A randomized, controlled study of rest vs. exercise showed that exercise did not change serum osteocalcin; other markers of formation increased transiently (each P &lt; 0.001): bone-specific alkaline phosphatase (+16.1%), carboxyterminal propeptide of type I procollagen (+14.1%), and procollagen III N-terminal extension peptide (+5.0%). The carboxyterminal cross-linked telopeptide of type I collagen, a bone resorption marker, increased 9.7% (P = 0.018) in response to exercise. A randomized, double blind, placebo-controlled, parallel study of recombinant human GH treatment (0.15 IU/kg·day) for 1 week increased serum osteocalcin (net increase preexercise, +10.0%; P = 0.017), carboxyterminal propeptide of type I procollagen (+17.6%; P = 0.002), procollagen III N-terminal extension peptide (+48.4%; P = 0.001), and carboxyterminal cross-linked telopeptide of type I collagen (53.3%; P = 0.009). Disappearance half-times after cessation of recombinant human GH for pre- and postexercise markers ranged from 248–770 h. We conclude 1) endurance exercise transiently activates bone and collagen turnover; 2) brief GH administration results in similar but quantitatively greater augmentation; and 3) these data will assist in designing a GH detection strategy.

Exercise increases the plasma membrane content of the Na+ -K+ pump and its mRNA in rat skeletal muscles

1996 ◽  
Vol 80 (2) ◽  
pp. 699-705 ◽  
Author(s):  
T. Tsakiridis ◽  
P. P. Wong ◽  
Z. Liu ◽  
C. D. Rodgers ◽  
M. Vranic ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Skeletal Muscles ◽  
Plasma Membranes ◽  
Acute Exercise ◽  
Treadmill Running ◽  
Type I ◽  
Mrna Levels ◽  
Subunit Mrna ◽  
White Type

Muscle fibers adapt to ionic challenges of exercise by increasing the plasma membrane Na+-K+ pump activity. Chronic exercise training has been shown to increase the total amount of Na+-K+ pumps present in skeletal muscle. However, the mechanism of adaptation of the Na+-K+ pump to an acute bout of exercise has not been determined, and it is not known whether it involves alterations in the content of plasma membrane pump subunits. Here we examine the effect of 1 h of treadmill running (20 m/min, 10% grade) on the subcellular distribution and expression of Na+-K+ pump subunits in rat skeletal muscles. Red type I and IIa (red-I/IIa) and white type IIa and IIb (white-IIa/IIb) hindlimb muscles from resting and exercised female Sprague-Dawley rats were removed for subcellular fractionation. By homogenization and gradient centrifugation, crude membranes and purified plasma membranes were isolated and subjected to gel electrophoresis and immunoblotting by using pump subunit-specific antibodies. Furthermore, mRNA was isolated from specific red type I (red-I) and white type IIb (white-IIb) muscles and subjected to Northern blotting by using subunit-specific probes. In both red-I/IIa and white-IIa/IIb muscles, exercise significantly raised the plasma membrane content of the alpha1-subunit of the pump by 64 +/- 24 and 55 +/- 22%, respectively (P < 0.05), and elevated the alpha2-polypeptide by 43 +/- 22 and 94 +/- 39%, respectively (P < 0.05). No significant effect of exercise could be detected on the amount of these subunits in an internal membrane fraction or in total membranes. In addition, exercise significantly increased the alpha1-subunit mRNA in red-I muscle (by 50 +/- 7%; P < 0.05) and the beta2-subunit mRNA in white-IIb muscles (by 64 +/- 19%; P < 0.01), but the alpha2- and beta1-mRNA levels were unaffected in this time period. We conclude that increased presence of alpha1- and alpha2-polypeptides at the plasma membrane and subsequent elevation of the alpha1- and beta2-subunit mRNAs may be mechanisms by which acute exercise regulates the Na+-K+ pump of skeletal muscle.

Gene Polymorphisms and Fiber-Type Composition of Human Skeletal Muscle

2012 ◽  
Vol 22 (4) ◽  
pp. 292-303 ◽  
Author(s):  
Ildus I. Ahmetov ◽  
Olga L. Vinogradova ◽  
Alun G. Williams
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Human Skeletal Muscle ◽  
Fiber Type ◽  
Vastus Lateralis Muscle ◽  
Type I ◽  
Fiber Types ◽  
Fiber Type Composition ◽  
Type Composition ◽  
Type I Fibers

The ability to perform aerobic or anaerobic exercise varies widely among individuals, partially depending on their muscle-fiber composition. Variability in the proportion of skeletal-muscle fiber types may also explain marked differences in aspects of certain chronic disease states including obesity, insulin resistance, and hypertension. In untrained individuals, the proportion of slow-twitch (Type I) fibers in the vastus lateralis muscle is typically around 50% (range 5–90%), and it is unusual for them to undergo conversion to fast-twitch fibers. It has been suggested that the genetic component for the observed variability in the proportion of Type I fibers in human muscles is on the order of 40–50%, indicating that muscle fiber-type composition is determined by both genotype and environment. This article briefly reviews current progress in the understanding of genetic determinism of fiber-type proportion in human skeletal muscle. Several polymorphisms of genes involved in the calcineurin–NFAT pathway, mitochondrial biogenesis, glucose and lipid metabolism, cytoskeletal function, hypoxia and angiogenesis, and circulatory homeostasis have been associated with fiber-type composition. As muscle is a major contributor to metabolism and physical strength and can readily adapt, it is not surprising that many of these gene variants have been associated with physical performance and athlete status, as well as metabolic and cardiovascular diseases. Genetic variants associated with fiber-type proportions have important implications for our understanding of muscle function in both health and disease.

scholarly journals Contractile activity-specific transcriptome response to acute endurance exercise and training in human skeletal muscle

2019 ◽  
Vol 316 (4) ◽  
pp. E605-E614 ◽  
Author(s):  
Daniil V. Popov ◽  
Pavel A. Makhnovskii ◽  
Elena I. Shagimardanova ◽  
Guzel R. Gazizova ◽  
Evgeny A. Lysenko ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Human Skeletal Muscle ◽  
Acute Exercise ◽  
Contractile Activity ◽  
Vastus Lateralis ◽  
Aerobic Exercise Training ◽  
Vastus Lateralis Muscle ◽  
Transcriptome Response ◽  
The One

Reduction in daily activity leads to dramatic metabolic disorders, while regular aerobic exercise training is effective for preventing this problem. The purpose of this study was to identify genes that are directly related to contractile activity in human skeletal muscle, regardless of the level of fitness. Transcriptome changes after the one-legged knee extension exercise in exercised and contralateral nonexercised vastus lateralis muscle of seven men were evaluated by RNA-seq. Transcriptome change at baseline after 2 mo of aerobic training (5/wk, 1 h/day) was evaluated as well. Postexercise changes in the transcriptome of exercised muscle were associated with different factors, including circadian oscillations. To reveal transcriptome response specific for endurance-like contractile activity, differentially expressed genes between exercised and nonexercised muscle were evaluated at 1 and 4 h after the one-legged exercise. The contractile activity-specific transcriptome responses were associated only with an increase in gene expression and were regulated mainly by CREB/ATF/AP1-, MYC/MAX-, and E2F-related transcription factors. Endurance training-induced changes (an increase or decrease) in the transcriptome at baseline were more pronounced than transcriptome responses specific for acute contractile activity. Changes after training were associated with widely different biological processes than those after acute exercise and were regulated by different transcription factors (IRF- and STAT-related factors). In conclusion, adaptation to regular exercise is associated not only with a transient (over several hours) increase in expression of many contractile activity-specific genes, but also with a pronounced change (an increase or decrease) in expression of a large number of genes under baseline conditions.

scholarly journals Hyaluronic acid, HAS1, and HAS2 are significantly upregulated during muscle hypertrophy

2012 ◽  
Vol 303 (5) ◽  
pp. C577-C588 ◽  
Author(s):  
Sarah Calve ◽  
Jahdonna Isaac ◽  
Jonathan P. Gumucio ◽  
Christopher L. Mendias
Keyword(s):  
Skeletal Muscle ◽  
Hyaluronic Acid ◽  
Type I Collagen ◽  
Muscle Growth ◽  
Type I ◽  
Muscle Adaptation ◽  
Cell Recruitment ◽  
Regeneration In Vitro ◽  
Muscle Progenitor Cell

Hyaluronic acid (HA) is a component of the extracellular matrix (ECM) in most vertebrate tissues and is thought to play a significant role during development, wound healing, and regeneration. In vitro studies have shown that HA enhances muscle progenitor cell recruitment and inhibits premature myotube fusion, implicating a role for this glycosaminoglycan in functional repair. However, the spatiotemporal distribution of HA during muscle growth and repair was unknown. We hypothesized that inducing hypertrophy via synergist ablation would increase the expression of HA and the HA synthases (HAS1–HAS3). We found that HA and HAS1–HAS3 were significantly upregulated within the plantaris muscle in response to Achilles tenectomy. HA concentration significantly increased 2.8-fold after 2 days but decreased towards levels comparable to age-matched controls by 14 days. Using immunohistochemistry, we found the colocalization of HAS1–HAS3 with macrophages, blood vessel epithelia, and fibroblasts varied in response to time and/or tenectomy. At the level of gene expression, only HAS1 and HAS2 significantly increased with respect to both time and tenectomy. The profiles of additional genes that influence ECM composition during muscle repair, tenascin-C, type I collagen, the HA-degrading hyaluronidases (Hyal) and matrix metalloproteinases (MMP) were also investigated. Hyal1 and Hyal2 were highly expressed in skeletal muscle but did not change after tenectomy; however, indicators of hypertrophy, MMP-2 and MMP-14, were significantly upregulated from 2 to 14 days. These results indicate that HA levels dynamically change in response to a hypertrophic stimulus and various cells may participate in this mechanism of skeletal muscle adaptation.

scholarly journals Coated-tube radioimmunoassay for C-telopeptides of type I collagen to assess bone resorption

1996 ◽  
Vol 42 (10) ◽  
pp. 1639-1644 ◽  
Author(s):  
M Bonde ◽  
C Fledelius ◽  
P Qvist ◽  
C Christiansen
Keyword(s):  
Bone Resorption ◽  
Postmenopausal Women ◽  
Type I Collagen ◽  
Premenopausal Women ◽  
Type I ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Analytical Recovery ◽  
Controlled Clinical Study ◽  
Different Doses

Abstract We present a coated-tube RIA that is useful for assessment of bone resorption. The assay uses a monoclonal antibody raised against a linear 8-amino-acid sequence (EKAHDGGR) derived from the C-telopeptides of type I collagen. Within-run and total CVs were 4.4% and 5.3-6.2%, respectively, at concentrations of 1-7 mg/L (n = 4-20). Analytical recovery was 98% +/- 8% and dilution 97% +/- 7%. Values obtained in a group of 36 premenopausal women were 227 +/- 89.6 mg/mol creatinine. In a group of 141 postmenopausal women, the values obtained were 429 +/- 225 mg/mol creatinine, a highly significant increase of 89% (P &lt;0.001) over the premenopausal value. In a double-blind placebo-controlled clinical study of these postmenopausal women receiving five different doses of a bisphosphonate, a significant decrease of RIA-measured C-telopeptide values was seen in all bisphosphonate-treated groups, after just 3 months. Values in urine samples from postmenopausal women assayed with the RIA (gamma) and the CrossLaps(TM) ELISA (x) agreed well: slope = 0.98 (95% confidence interval, 0.94-1.01), intercept = 0.34 (0.25-0.43) mg/L, and Sylx = 0.93 mg/L (n = 678). We conclude that this RIA represents a valuable tool for assessing bone resorption.

scholarly journals Skeletal muscle fiber type-selective effects of acute exercise on insulin-stimulated glucose uptake in insulin-resistant, high-fat-fed rats

2019 ◽  
Vol 316 (5) ◽  
pp. E695-E706 ◽  
Author(s):  
Mark W. Pataky ◽  
Carmen S. Yu ◽  
Yilin Nie ◽  
Edward B. Arias ◽  
Manak Singh ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Acute Exercise ◽  
Fiber Type ◽  
Single Fiber ◽  
Male Rats ◽  
Type I ◽  
Fiber Types ◽  
High Fat ◽  
Insulin Resistant

Insulin-stimulated glucose uptake (GU) by skeletal muscle is enhanced several hours after acute exercise in rats with normal or reduced insulin sensitivity. Skeletal muscle is composed of multiple fiber types, but exercise’s effect on fiber type-specific insulin-stimulated GU in insulin-resistant muscle was previously unknown. Male rats were fed a high-fat diet (HFD; 2 wk) and were either sedentary (SED) or exercised (2-h exercise). Other, low-fat diet-fed (LFD) rats remained SED. Rats were studied immediately postexercise (IPEX) or 3 h postexercise (3hPEX). Epitrochlearis muscles from IPEX rats were incubated in 2-deoxy-[3H]glucose (2-[3H]DG) without insulin. Epitrochlearis muscles from 3hPEX rats were incubated with 2-[3H]DG ± 100 µU/ml insulin. After single fiber isolation, GU and fiber type were determined. Glycogen and lipid droplets (LDs) were assessed histochemically. GLUT4 abundance was determined by immunoblotting. In HFD-SED vs. LFD-SED rats, insulin-stimulated GU was decreased in type IIB, IIX, IIAX, and IIBX fibers. Insulin-independent GU IPEX was increased and glycogen content was decreased in all fiber types (types I, IIA, IIB, IIX, IIAX, and IIBX). Exercise by HFD-fed rats enhanced insulin-stimulated GU in all fiber types except type I. Single fiber analyses enabled discovery of striking fiber type-specific differences in HFD and exercise effects on insulin-stimulated GU. The fiber type-specific differences in insulin-stimulated GU postexercise in insulin-resistant muscle were not attributable to a lack of fiber recruitment, as indirectly evidenced by insulin-independent GU and glycogen IPEX, differences in multiple LD indexes, or altered GLUT4 abundance, implicating fiber type-selective differences in the cellular processes responsible for postexercise enhancement of insulin-mediated GLUT4 translocation.

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