Resistance training induced increase in muscle fiber size in young and older men.

Muscle strength and mass decline in sedentary individuals with aging. The present study investigated the effects of both age and 21 weeks of progressive hypertrophic resistance training (RT) on skeletal muscle size and strength, and on myostatin and myogenin mRNA expression in 21 previously untrained young men (26.0 ± 4.3 years) and 18 older men (61.2 ± 4.1 years) and age-matched controls. Vastus lateralis muscle biopsies were taken before and after RT. Type I and type II muscle fiber cross-sectional areas increased more in young men than in older men after RT (P < 0.05). Concentric leg extension increased (P < 0.05) more after 10.5 weeks in young men compared to older men, but after 21 weeks no statistical differences existed. The daily energy and protein intake were greater (P < 0.001) in young subjects. Both myostatin and myogenin mRNA expression increased in older when compared with young men after RT (P < 0.05). In conclusion, after RT, muscle fiber size increased less in older compared to young men. This was associated with lower protein and energy intake and increases in myostatin gene expression in older when compared to young men.

Muscle strength, resting muscle tone and EMG activation in untrained men: interaction effect of time of day and test order-related confounding factors.

AIM: This article was designed to study an interaction effect of time of day and test order-related confounding factors on daily variation in maximum muscle strength and power. METHODS: Seventeen untrained men were randomized into four groups and measured at four time points (08:00 a.m., 12:00 a.m., 04:00 p.m. and 08:00 p.m.) throughout one or two days. Each groups started at different time of day in a counter-balanced order. Peak force and myoelectrical activity (EMG) of vastus medialis, vastus lateralis and biceps femoris muscles during bilateral isometric leg extension and power output during explosive dynamic leg extension was measured. Computerized muscle tonometer was used to assess resting muscle tone. RESULTS: Resting muscle tone did not change significantly regardless of time of day or test order. In contrast, time-of-day effect was found in force and EMG during isometric leg extension and in power output; all variables were significantly lower in the morning compared to the individual best performance/highest value achieved at any time point. In addition, the above variables were also affected by test order. Regardless of time of day, isometric force and EMG were typically highest during the first test session, while the dynamic power output gradually improved with test order. CONCLUSION: Daily variation in maximum voluntary strength and power performance could be detected despite the test order-related confounding factors.

Heat shock protein 90 and the nuclear transport of progesterone receptor.

Steroid receptors exist as large oligomeric complexes in hypotonic cell extracts. In the present work, we studied the nuclear transport of the 2 major components of the oligomeric complex, the receptor itself and the heat shock protein 90 (Hsp90), by using different in vitro transport systems: digitonin permeabilized cells and purified nuclei. We demonstrate that the stabilized oligomeric complex of progesterone receptor (PR) cannot be transported into the nucleus and that unliganded PR salt dissociated from Hsp90 is transported into the nucleus. When nonstabilized PR oligomer was introduced into the nuclear transport system, the complex dissociated and the PR but not the Hsp90 was transported into the nucleus. If PR exists as an oligomeric form after synthesis, as suggested by the experiments with reticulocyte lysate, the present results suggest that the complex is short-lived and is dissociated before or during nuclear transport. Thus, the role of Hsp90 in PR action is likely to reside in the Hsp90-assisted chaperoning process of PR preceding nuclear transport of the receptor.

Only a small portion of the cytoplasmic progesterone receptor is associated with Hsp90 in vivo.

In cell extracts all of the nonliganded steroid receptor molecules are found as an oligomeric complex with Hsp90 and other proteins. In previous studies we have shown that Wild-type Hsp90 and progesterone receptor (PR) are located in different cell compartments (Tuohimaa et al. [1993] Proc. Natl. Acad. Sci. USA 90:5848-5852). In the present work we studied whether PR and Hsp90 can efficiently associate provided they are present in the same cell compartment. The association of Hsp90 with PR in vivo was studied by nuclear cotranslocation and immunohistochemistry with an antibody (alphaD) which can distinguish between the oligomeric and dissociated form. Upon expression of a cytoplasmic mutant of PR with Wild-type (cytoplasmic) Hsp90 and Wild-type (nuclear) PR with NLS-Hsp90 (a Hsp90 with a nuclear localization signal), we noted that the epitope of alphaD in PR was exposed in both cases. Also, in vivo crosslinking and treatment of cells with substances which stabilize the oligomeric complex in vitro were inefficient in demonstrating or inducing a similar oligomeric receptor form detectable in vitro in cell homogenates. However, when the cytoplasmic PR mutant (DeltaPR) was coexpressed with a nuclear form of Hsp90 (NLS-Hsp90), a portion of PR was cotranslocated into the nucleus. This would indicate that steroid receptors are indeed associated with Hsp90 in intact cells, but the Hsp90-associated receptor pool represents only a small portion of the receptors. This suggests that the majority of oligomeric complexes seen in cell extracts are formed during cell fractionation.

Reappraisal of the role of heat shock proteins as regulators of steroid receptor activity.

Almost 30 years have passed since the original demonstration that steroid receptors, comprising a subfamily of the nuclear receptor (NR) superfamily, exist as large (6-8S) non-DNA-binding complexes in hypotonic extracts (cytosol) of target cells; later such complexes were shown to correspond to a heterooligomer composed of receptor, heat shock (Hsp), and other proteins. Subsequently, an impressive number of studies have dealt with the composition of the "nonactive" complex, its dissociation and/or reassembly in vitro, possible functions of the non-receptor components, and their subcellular compartmentalization. While there is little dispute about the chaperoning role of some Hsps in such a complex, there is still no final proof of an association in vivo of NRs and Hsps in the nuclei of target cells, which is requisite for a direct regulatory involvement of Hsps in NR function. Here we critically review the various models that have been put forward to attribute a biological function to the NR-Hsp90 interaction, evaluate the corresponding experimental data, and integrate recent concepts originating from the structural and functional analyses of NRs.