NCT03054168

Systemic Hormones and Muscle Protein Synthesis

The Regulation of Skeletal Muscle Protein Synthesis by Systemic Hormones and Its Influence on Ageing and Anabolic Resistance

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 34 (actual)
• Sponsor: University of Nottingham · Academic / Other
• Sex: Male
• Age: 18 Years – 75 Years
• Healthy volunteers: Accepted

Summary

This study evaluates the effect of increase in testosterone levels in older males and the effects of decrease in testosterone levels in young males on muscle protein synthesis.

Detailed description

Skeletal muscle represents the largest organ in the body, comprising \>50% of total body mass. The function of skeletal muscle is best understood for its role in locomotion and providing mechanical support to the skeleton to facilitate movement. However, skeletal muscles are also important for maintaining whole-body metabolic health. For example, muscles also act as a site for glucose disposal thereby acting to maintain whole-body glycaemic control. In addition, skeletal muscles represent a vast protein store, the amino acids from which can be used in times of fasting, infection and disease to provide energy to maintain other critical organs. Exercise (resistance type exercise (RE-T) in particular) still remains the most effective means by which to maintain and increase muscle mass through stimulation of muscle protein synthesis (MPS), despite this, how exercise regulates these changes in muscle mass is still unknown. A number of pathways have been inferred as key, however it is clear from a number of studies that systemic hormone levels, testosterone in particular, may provide a significant contribution. It is well known that chronic androgenic hormone deficiency can lead to a loss of lean body mass and strength, which can in turn contribute to impaired physical function. Furthermore, when testosterone levels are pharmacologically reduced (using a gonadotropin releasing hormone analogue) in healthy young males, resistance exercise training induced increases in muscle mass and strength are absent. Whilst systemic hormone levels are carefully maintained in youth (unless illness or deficiency is present), levels of these hormones decrease with age, particularly in those that are not regularly physically active, indeed approximately 25-30% of older men have levels of testosterone which are below the threshold used to define hypogonadism. Therefore, there is significant need to understand the underlying mechanisms behind hormonally induced muscle mass regulation. Furthermore, in older age there is a resistance to traditional anabolic stimuli such as nutrition or resistance exercise, with older adults showing a blunted-anabolic hormonal profile in response to resistance training compared to young. These impairments to hormonal regulation with ageing may in part be responsible for the slow decline in muscle mass with age known as sarcopenia. Whilst all muscle-wasting conditions are of considerable concern, it is the loss of muscle in older age that poses the greatest socio-economic burden. Therefore there is a significant clinical need to identify contributing factors to this muscle loss so that they can be specifically targeted for intervention (i.e., pharmacological hormonal therapies). The aims of this project are two fold: 1) Firstly we aim to investigate the impact of systemic hormone levels on control of muscle mass in healthy young adults undertaking a resistance exercise training program, we hypothesize that reduction of hormone levels in systemically normal young adults will impair MPS and muscle mass gains in response to resistance exercise training. 2) Secondly we aim to investigate the impact of enhancing testosterone levels in older adults on responsiveness to resistance exercise training and the contribution of systemic testosterone levels to muscle mass regulation in ageing, we hypothesize that increasing testosterone levels in older males will improve responsiveness to anabolic stimuli (RE-T).

Conditions

• Sarcopenia
• Muscle Hypotrophy
• Muscle Atrophy

Interventions

Type	Name	Description
DRUG	Sustanon 250	The frequency of the injection will be every 2 weeks, 250mg of testosterone, intramuscular injection.
DRUG	Zoladex	The frequency of the injection will be just one injection, 3.6 mg of Zoladex, Subcutaneous injection (abdomen).
OTHER	Placebo

Timeline

• Start date: 2016-12-15
• Primary completion: 2018-11-15
• Completion: 2019-02-15
• First posted: 2017-02-15
• Last updated: 2019-02-26

Locations

1 site across 1 country: United Kingdom