The traditional view of skeletal muscle focuses primarily on its mechanical role: contracting to produce force, movement, and posture. However, muscle also performs a profound biological function. The answer to whether muscles secrete hormones is definitively yes, redefining muscle as a sophisticated signaling organ. These secreted messenger molecules are collectively known as myokines, which are peptides and proteins released by muscle fibers in response to activity. Muscle tissue acts as a major endocrine gland, using myokines to regulate health, metabolism, and the function of distant organs.
The Endocrine Role of Muscle Tissue
The recognition of muscle as a secretory organ represents a significant shift from the historical understanding of its biology. This new view places skeletal muscle alongside traditional glands like the thyroid and pancreas in its capacity to produce and release hormones. Researchers formally introduced the term “myokines” in 2003 after observing that contracting muscle released molecules into the bloodstream that could influence other tissues. Myokines operate through three primary signaling pathways:
Signaling Pathways
- Endocrine signaling occurs when a myokine travels through the bloodstream to exert its effect on a distant organ, such as the liver or brain.
- Paracrine signaling involves myokines acting locally on neighboring cells, such as satellite cells or blood vessels, within the muscle tissue itself.
- Autocrine signaling is the most localized, where the myokine acts back upon the muscle fiber that produced and secreted it.
This complex communication network allows muscle to coordinate systemic energy balance and adaptive responses to physical demands.
Key Myokines and Their Specific Functions
A growing list of hundreds of myokines has been identified, each with distinct effects on bodily systems.
Irisin
The myokine Irisin is noted for its role in energy expenditure and metabolic health. Irisin acts on white adipose tissue, stimulating “browning,” which converts energy-storing white fat cells into beige fat cells. These beige cells burn energy to produce heat, increasing overall caloric expenditure.
Interleukin-6 (IL-6)
Interleukin-6 (IL-6) was the first protein identified to be released by contracting muscle fibers. When released acutely during exercise, IL-6 functions as a metabolic regulator. It promotes the breakdown of fat (lipolysis) and increases glucose uptake in muscle. This muscle-derived IL-6 helps mobilize energy stores to fuel working muscles and exerts a systemic anti-inflammatory effect.
Myostatin
In contrast to these beneficial molecules, Myostatin acts as a negative regulator of muscle growth. It limits muscle hypertrophy by inhibiting the proliferation of muscle stem cells and suppressing protein synthesis. Myostatin’s function is to maintain homeostatic balance by preventing excessive muscle mass accumulation. Exercise typically suppresses Myostatin secretion, creating an environment conducive to muscle repair and growth.
The Trigger: How Exercise Stimulates Secretion
The release of myokines is tightly regulated and primarily stimulated by muscle contraction during physical activity. The two main physiological triggers are mechanical stress and metabolic stress within the cell. The mechanical force of muscle fibers pulling against resistance leads to internal cellular signals that initiate myokine production and release.
This mechanical stimulation is linked to subsequent metabolic changes as the muscle demands energy. Muscle activity causes a rapid increase in the ratio of AMP to ATP, which activates the master metabolic sensor called AMP-activated protein kinase (AMPK). This metabolic signaling is a potent trigger for myokines like Irisin, which are involved in energy homeostasis. Furthermore, the surge in intracellular calcium necessary for muscle contraction acts as a second messenger, directly stimulating the secretion of myokines such as IL-6.
The specific myokine profile released varies depending on the type and intensity of exercise. Endurance exercise favors the sustained release of metabolic regulators like Irisin and IL-6. Conversely, resistance training suppresses Myostatin and elevates factors that promote muscle repair and growth. This difference allows the muscle to tailor its systemic communication to the specific physiological challenge.
Systemic Impact of Muscle Signaling
The myokine system facilitates a widespread communication network between muscle and other major organ systems. This signaling is central to mediating the health benefits associated with regular physical activity.
Muscle-Adipose Tissue
Communication between muscle and adipose tissue is important for metabolic health. Myokines improve insulin sensitivity in fat cells and help regulate fat distribution, contributing to a reduced risk of conditions like type 2 diabetes.
Muscle-Liver Axis
Myokines also engage the liver, regulating both glucose and lipid metabolism. They modulate the liver’s production of glucose and promote the oxidation of fatty acids, which maintains energy balance. This axis helps maintain stable blood sugar levels and prevents fat accumulation in the liver.
Muscle-Brain Connection
The muscle-brain connection shows that myokines influence neurocognitive function. Myokines like Irisin cross the blood-brain barrier, where they promote the expression of brain-derived neurotrophic factor (BDNF). BDNF supports the survival and growth of neurons. This signaling pathway contributes to improved mood, enhanced cognitive function, and protection against age-related cognitive decline.