Androgen receptors and testosterone in men—Effects of protein ingestion, resistance exercise and fiber type

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Abstract

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.

Introduction

The process of muscle hypertrophy is known to be regulated by mechanical, hormonal and nutritional signals. Growth factors or hormones such as testosterone and insulin-like growth factor I (IGF-I) are potent anabolic agents. Testosterone is an endogenously secreted androgen that interacts with skeletal muscle cells via binding to androgen receptors (AR) [1], [2]. The importance of androgens on human skeletal muscle is underscored by findings showing that physiological levels of androgens are necessary for normal adaptations in muscle size and strength to occur with strength training [3] and that supraphysiological levels augment the adaptive response in muscle mass to strength training [4]. Moreover, the electrical stimulation induced increase in muscle mass was effectively suppressed by the androgen receptor blockade in rats [5]. Additionally, the importance of insulin like growth factor-I (IGF-I) for muscle growth has been shown in many in vivo and in vitro studies [6], [7], [8]. Androgen administration is shown to increase mRNA levels of IGF-I [9], [10] and therefore IGF-I pathway may play a role in androgen-mediated muscle growth [10]. IGF-I exists as three splice variants, i.e. IGF-IEa, IGF-IEb and IGF-IEc (MGF: mechano growth factor) [11], from which MGF is muscle specific.

The AR expression is affected by environmental factors such as training state and nutrition, and possibly muscle fiber type. For instance, different short-term [12], [13], [14] and long-term [15] resistance exercise (RE) regimens as well as possibly nutrition [16] and androgen use [15] have been shown to affect AR content in the skeletal muscle of young humans, but this has not been studied in older people. Also the levels of testosterone, the AR ligand, in the blood are affected by exercise. An acute bout of RE transiently elevates testosterone levels, but this response is attenuated with pre- or post-exercise feeding, at least in young men [16], [17], [18], [19]. The expression of muscle MGF or IGF-IEa, can be affected by both a single RE bout [12] and long-term strength training [20]. It remains, however, unclear whether feeding before and after a workout, especially protein such as whey, would affect blood testosterone and muscle AR, MGF and IGF-IEa expression in older men. Interestingly, apparently greater exogenous androgen-induced increases in muscle size have been observed in slow-twitch type-I muscle fibers compared to fast-twitch type-II fibers [21], [22], [23], [24], [25]. Variability in the responsiveness of skeletal muscles to androgens may reflect differential expression or localization of AR between different types of muscles [15], [26].

This study was undertaken to study the effects of RE bout with or without protein ingestion before and after a RE bout on blood testosterone, and on muscle AR, MGF and IGF-IEa gene expression in older men who had a standardized training background during the last 5 months. Consequently, we had the study subjects well familiarized with the performance of RE bout. Moreover, considering the suggested greater sensitivity of type-I human muscle fibers to androgens, the AR location and also robust amount was compared via immunohistochemical stainings of ARs as well as MyHC I and MyHC II, specific for type I and type II muscle fibers, respectively.

Section snippets

Experimental design

The acute effects of protein nutrition before and after RE bout were investigated with older men. In this RE study, after 5 months of supervised strength training in a larger project, a subsample was identified who were willing to take part in the present study. These subjects were matched according to age, body mass and maximal 1RM strength, and then randomly assigned to either a whey protein (n = 9) or a placebo (n = 9) group (see Table 1 and Fig. 1). Accordingly, the previous training experience

Resistance exercise bout and dietary diaries

The total volume of the RE work (loads × sets × repetitions, means ± S.D.) was similar in the placebo (7572 ± 1105 kg) and in the protein group (8094 ± 1378 kg). Borg's subjective rate of perceived exertion and blood lactates were similar following the RE bout in the placebo (17.0 ± 0.6 and 9.9 ± 0.4 mmol/l) compared to the protein group (16.9 ± 0.5 and 9.7 ± 1.2 mmol/l. Maximal isometric leg extension force decreased significantly (P < 0.01) and similarly following the RE bout in both the placebo (28%, from 2874 ± 352

Discussion

The present study showed that protein ingested before and after a single resistance exercise (RE) bout in older men attenuated serum free and total testosterone response to RE bout comparably to the changes found earlier for total testosterone with younger men [18]. We also showed here that even in older men, RE bout can provide a stimulus for up-regulation of muscle AR mRNA expression. However, protein ingestion did not significantly affect AR mRNA and protein levels or MGF and IGF-IEa mRNA

Acknowledgements

The authors thank Tuomas Kaasalainen, Tuovi Nykänen, Risto Puurtinen, Aila Ollikainen, Tiina Salo, Inna Lisko, Aura Peltonen and Paavo Rahkila for their help in data collection or analysis used. We also thank the very dedicated group of subjects who made this project possible. We thank Härmä Food Ltd. for providing the drinks. Finnish Ministry of Education and the Finnish Cultural Foundation supported this research. The monoclonal antibodies A4.951 and A4.74 developed by Dr. Blau [36] was

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