Serum IGF-I, IGFBP-3 and ALS concentrations and physical performance in young swimmers during a training season.

INTRODUCTION: The GH/IGF-I axis is a system of growth mediators, receptors, and binding proteins that regulate somatic and tissue growth; and it has been shown that exercise programs are related to the anabolic function of this axis. OBJECTIVE: The aim of this study was to analyse the changes of serum IGF-I concentration and that of its binding proteins IGFBP-3 and ALS in adolescent swimmers at different stages of a training season, and compare them with physical performance parameters and body composition of the athletes. MATERIAL AND METHODS: Nine male athletes, aged 16 to 19years and who trained regularly throughout the season, were included in this study. Serum IGF-I, IGFBP-3, and ALS concentrations were recorded before and after (pre×post) standardized training sessions during the different stages of a training season (extensive×intensive×tapering). Endurance in freestyle, anaerobic fitness in tied swimming (Peak Force and Average Force), body mass, fat percentage, and lean body mass were also analysed at the different stages of training in order to compare the changes of the IGF-I/IGFBP/ALS system with the physical performance and body composition of the athletes. Variations in the IGF-I/IGFBP-3-ALS system before and after a standardized training session, and at the different stages of training were analysed by the Wilcoxon and Friedman non-parametric tests, respectively. Significance was considered at 5%. RESULTS: The results from this study demonstrate that IGF-I is sensitive to the acute and chronic effects of training, exhibiting biphasic behaviour throughout the season. The catabolic phase was characterized by a reduction in serum IGF-I concentrations during the intensive stage (∆IGF-I: - 43.33±47.32ng/ml; P<0.05) while the anabolic phase was marked by similar basal concentrations at the different stages of training and an increase in post-training serum IGF-I concentrations during the tapering stage (320±40; 298±36 and 359±94ng/ml; P<0.05). IGFBP-3 was only sensitive to the chronic effects of training, with a reduction in post-training serum concentrations during the intensive stage and an increase during the tapering stage (4.7±0.7, 4.6±0.4 and 5.0±0.7mg/l; P<0.05). No significant difference (P>0.05) was observed in pre- or post-training IGFBP-3 concentrations (∆IGFBP-3) at the different stages. ALS concentrations remained unchanged throughout the season, demonstrating that in adolescent athletes they are unaffected by the acute or chronic effects of swimming. Peak Force (25.0±6.3, 24.2±5.7 and 28.5±6.5N; P<0.05) and Average Force (10.3±3.6, 8.8±1.8 and 14.7±1.8N; P<0.05) followed IGF-I and IGFBP-3 variations, with a decrease during the intensive stage and a significant (P<0.05) increase during the tapering stage. The body composition and cardiorespiratory condition of the swimmers did not vary significantly throughout the season, exhibiting behaviour independent of IGF-I or IGFBP-3. CONCLUSION: Serum IGF-I and IGFPB-3 concentrations have proven to be sensitive markers of training status and, thus, may be used as guides for coaches and athletes in the challenging task of modulating training intensity in young athletes.

Cyclic adenosine monophosphate (cAMP) increases natriuretic peptide receptor C (NPR-C) expression in human aortic smooth muscle cells.

Activation of the intracellular cAMP-signaling pathway by either forskolin or the cAMP-mimetic dibutyryl cAMP significantly increased transcript levels of NPR-C in primary cultures of human aortic smooth muscle cells. The time course of the increase was rapid, with significant differences from control occurring within 3 h of treatment and reaching approximately 6 times control value after 24 h of exposure to 10 microM forskolin. Expression levels of the natriuretic peptide receptor B (NPR-B), but not the natriruetic peptide receptor A (NPR-A) were also increased by forskolin, rising to a level of approximately 2 times control at 96 h. NPR-B transcript levels in the presence of dibutyryl cAMP were unaltered by the protein kinase A (PKA) inhibitor KT-5720, suggesting a PKA-independent pathway to NPR-B up-regulation. In contrast, KT-5720 reduced NPR-C transcript to a lower level that was not significantly different from control. Partial re-differentiation of AOSMC by culture in growth factor-reduced matrix (Matrigel) did not significantly change NPR-C transcript levels compared with cells grown on plastic, and the dibutyryl cAMP-induced increase in NPR-C (approximately eight-nine-fold control value) was retained. The dibutyryl cAMP/forskolin effect on NPR-C transcript was not reproduced by the beta2-selective adrenergic agonist isoproterenol (10 microM), but was replicated by incubation with the phosphodiesterase inhibitor isobutylmethylxanthine (0.5 mM). Up-regulated NPR-B and NPR-C transcript levels were reflected, respectively, in a two-fold increase in CNP-stimulated cGMP and an increase in 125I-ANF binding competed by the NPR-C-specific natriuretic peptide, C-ANF(4-23) following a 4-day treatment with 0.125 mM dbcAMP. The present data suggest that elevation of cAMP in human vascular smooth muscle may potentiate the vasoactive effects of natriuretic peptides acting through the NPR-B and NPR-C receptors.

cAMP inhibits natriuretic peptide receptor-B activity and increases C-type natriuretic peptide in FRTL-5 rat thyroid cells.

C-type natriuretic peptide (CNP) and its cognate guanylyl cyclase receptor, the natriuretic peptide receptor B (NPR-B) together constitute a regulatory system that controls cell function via the generation of intracellular cyclic GMP. In this report we have examined the role of cAMP signaling in the regulation of CNP and NPR-B activity in the FRTL-5 rat thyroid follicular cell line. As had been observed earlier with TSH, the cAMP mimetic, dibutyryl cAMP (dbcAMP; 1 mM) induced a significant reduction in CNP-stimulated cGMP generation that was first apparent after 6 h of treatment. The inhibitory effect of dbcAMP on NPR-B was dose dependent, with an EC50 of 0.2 mM. Pretreatment of FRTL-5 cells with either of two protein kinase A (PKA) inhibitors, KT-5720 and H-89, failed to curtail the dbcAMP reduction in NPR-B activity, suggesting that the cAMP pathway leading to inhibition of NPR-B is PKA independent. Whereas either a 30-min or a 24-h treatment with the protein kinase C-activator phorbol myristate acetate failed to alter maximal levels of CNP-stimulated cGMP, a 24-h exposure to the calcium ionophore A23187 reduced CNP-stimulated cGMP to about one-third of control. Pretreatment of FRTL-5 cells with the cell-permeable calcium chelator 1,2 bis(2-aminophenoxy)ethane-N,N,N1,N1-tetraacetic acid, tetraacetoxymethyl ester completely abrogated the cAMP-induced reduction of CNP-stimulated cGMP. Real-time PCR showed no effect of dbcAMP on NPR-B transcript at 3 and 6 h, but indicated a 40% reduction in transcript by dbcAMP at 24 h. In contrast, real-time PCR indicated a 5-fold increase in CNP transcript at 3 h, reaching 15.4-fold above control at 6 h in cells treated with dbcAMP. In addition, immunofluorescence staining of FRTL-5 cells with a specific antibody for CNP-22 showed the presence of cytoplasmic CNP that was up-regulated by incubation with either TSH or dbcAMP. These results suggested that cAMP signaling regulates the natriuretic peptide system in rat thyroid cells by increasing CNP expression, and reducing NPR-B activity. This latter action of cAMP appears to be both PKA independent and calcium dependent, and provides support for a dominant role for calcium in the regulation of NPR-B in the rat thyroid.