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The complete guide to protein anabolism and catabolism

Der vollständige Ratgeber zum Thema Protein Anabolismus und Katabolismus

After describing the basics of protein metabolism and the effects of insulin and IGF-1 on it in the first part of this article, in this second part we will take a closer look at the influence of growth hormones, androgens, oestrogens, thyroid hormones and stress hormones on protein metabolism.

Growth hormones

Growth hormones are peptide hormones that are produced in the pituitary gland and stimulate cellular growth and cellular reproduction. When the body is well nourished, growth hormones stimulate the production of insulin in the pancreas and IGF-1 in the liver, which subsequently stimulates the growth of lean body tissue and adipose tissue, as well as the storage of glucose. During fasting or other catabolic states, growth hormones stimulate the release and oxidation of fatty acids for the purpose of providing energy to the body, thus protecting lean body mass and glycogen stores (11).

Growth hormones appear to be the most misunderstood hormones in the human body. Some so-called "fitness gurus" claim that these hormones are neither anabolic nor do they make sense from a health perspective (which are quite arrogant claims considering the scientific research that shows the opposite). Growth hormones do indeed have a number of anabolic effects in the human body, but these are mechanistically different from those of insulin. Growth hormone could be considered the primary anabolic hormone during stress and fasting, whereas insulin is the primary anabolic hormone during the post-fasting window.

Scientific research has shown that growth hormones strongly inhibit amino acid oxidation (remember that amino acids can be burned for energy). Thus, growth hormones protect the amino acid pool from depletion, resulting in a higher availability of amino acids for incorporation into proteins (11).

Growth hormones appear to alter whole body protein synthesis in the short term and any increases in muscle protein synthesis due to growth hormone release are also likely to result in subsequent local IGF-1 release. Both growth hormone and testosterone (which we will discuss later) increase local IGF-1 levels, which can promote anabolic effects in skeletal muscle tissue.

Surprisingly, scientific studies have shown that exogenous administration of IGF-1 suppresses local IGF-1 production in muscle tissue, resulting in no increase in muscle protein synthesis (7, 12, 13). Thus, the use of IGF-1 as a performance-enhancing substance appears to be useless when it comes to increasing muscle growth.

It has been shown that growth hormones not only promote protein synthesis but also inhibit protein degradation and it is likely that this effect is due to local production of IGF-1 in muscle tissue (14). The reason for attributing the anabolic effects to growth hormones is quite simple, as growth hormones cause an increase in IGF-1 production.

A final point to consider regarding the anabolic effects of growth hormones is that growth hormones accelerate the transport of certain essential amino acids across the cell membrane, which is particularly true for amino acids transported via system L - the primary transport system responsible for sodium-independent transport of neutral amino acids such as leucine, isoleucine and valine (15).

Growth hormone summary:

Growth hormones are highly complex hormones that are under intense investigation as many of its in vivo actions are not yet fully understood.

In summary, growth hormones are potent hormones that promote body-wide protein synthesis and reduce body-wide protein degradation - and it is likely that these effects also occur in skeletal muscle tissue once growth hormone-induced local IGF-1 production begins (it is hoped that further studies will be conducted on this topic in the coming years).

Growth hormones also strongly inhibit amino acid oxidation and increase the transmembrane transport of amino acids such as the branched-chain amino acids leucine, isoleucine and valine. In addition, it should be noted that growth hormones strongly influence fat loss, as they promote the use of fatty acids for the purpose of supplying the body with energy.

As mentioned in the IGF-1 section, numerous factors are involved when it comes to when and how much growth hormone is released. Since growth hormone is secreted in a pulsatile manner (with approximately 50% of the total amount of growth hormone secreted daily being secreted during sleep), it makes sense to consider the following factors that stimulate and inhibit growth hormone production:

Factors that stimulate growth hormone secretion (16-22):

  • Sex hormones (androgens and oestrogens)
  • Peptide hormones such as ghrelin and growth hormone-releasing hormone (GHRH)
  • L-DOPA, the precursor of the neurotransmitter dopamine
  • Nicotinic acid (vitamin B3)
  • Nicotine receptor agonists
  • Somatostatin inhibitors
  • Fasting
  • Deep sleep
  • Intensive training

Factors that inhibit growth hormone secretion (18, 23-26):

  • Somatostatin
  • Hyperglycemia(carbohydrates in the bloodstream)
  • IGF-1 and growth hormone (due to negative feedback inhibition of the pituitary gland)
  • Xenobiotics
  • Glucocorticoids
  • Certain sex hormone metabolites such as dihydrotestosterone (DHT)

Androgens

Many readers will probably be familiar with the term anabolic androgenic steroid, which is often used in the media and fitness subculture. This already tells you that androgens are indeed anabolic hormones - and they influence the development and maintenance of the male sexual organs, as well as the characteristics of the male sex.

Several different androgens are produced in the human adrenal glands, but the primary androgen we will focus on here is the male sex hormone also known as testosterone (produced primarily in the testes in men and ovaries in women), as it is the body's most potent natural anabolic steroid.

There is a significant amount of research showing that this hormone plays a leading role in the growth and maintenance of skeletal muscle. In studies where men suffering from testicular hypofunction were given a replacement amount of this androgen, it was observed that lean body mass, skeletal muscle strength and muscle protein synthesis increased dramatically (27, 28, 29). These effects have also been observed in trained athletes and normal, healthy men following the administration of pharmacological doses of various androgens (30, 31).

It appears that androgens, like growth hormones, exert some of their anabolic effects by reducing amino acid oxidation (particularly leucine) and increasing the uptake of amino acids into body proteins, including muscle proteins (32).

In addition, there appears to be a synergistic (but independent) anabolic effect between testosterone and growth hormones, which mutually reinforce their benefits on skeletal muscle protein synthesis (33).

Androgen Summary:

There are many reasons that the primary male sex hormone and other androgens are being studied so intensively and it is quite clear that these compounds have a variety of anabolic effects in the human body. Primary male androgen is a potent inhibitor of amino acid oxidation and increases body-wide protein synthesis including skeletal muscle protein synthesis (and also appears to have anti-proteolytic effects (34).

As with growth hormone and IGF-1, many factors play a role in regulating the production of this androgen. Below is an abbreviated list of these variables.

Factors that positively influence androgen production/levels (35-40):

  • Adequate amounts of sleep
  • Fat loss (to a certain extent, as fat cells secrete the aromatase enzyme that converts androgens to estrogen)
  • Intense exercise (especially resistance training)
  • D-aspartic acid supplementation
  • Vitamin D supplementation
  • Abstinence (for about a week at a time)

Factors that negatively affect androgen production (26, 38, 39, 41-43):

  • Obesity/overweight
  • A lack of sleep
  • Diabetes (especially insulin-resistant/type 2 diabetes)
  • A sedentary lifestyle / inactivity
  • Very low-fat diets
  • Prolonged aerobic activity
  • Excessive alcohol consumption
  • Xenobiotics

Estrogenic hormones

Oestrogens are the basic female sex hormones and are responsible for the growth and maturation of female reproductive tissue - but they are also present in the male body (albeit in lower concentrations). Three primary oestrogens are produced in the human body: oestradiol, oestrone and oestriol. Oestradiol is about ten times more potent than oestrone on a molecular basis and 80 times more potent than oestriol in terms of oestrogen effect.

In women, most oestrogens are produced in the ovaries via aromatization of androstenedione, while in men it is produced in small amounts in the testes and to a greater extent via aromatization of testosterone in the fat cells.

Unlike all the other hormones we have looked at so far, estrogen appears to have both anabolic and catabolic properties when it comes to protein metabolism (mainly by influencing other hormones in the body).

Studies have shown that estrogens can increase growth hormone levels and local IGF-1 levels, both of which have positive effects on protein anabolism and anticatabolism. (44, 45, 46). In addition, estrogens promote water retention, which is beneficial for cell volumization and thus anabolism.

When excessive amounts of estrogen are present, it can have an indirect catabolic effect via blockade of androgen receptors and downregulation of gonadotropin-releasing hormone production in the hypothalamus, which ultimately decreases androgen production in the body.

Estrogen Summary:

As with many other things in the health and fitness world, there is a balance to be found with estrogen levels. Estrogens have many important effects in the human body and even some anabolic/anti-catabolic effects on protein metabolism.

However, you should be careful, as excessive estrogen levels (especially in men) are likely to decrease androgen production and availability, thereby interfering with the positive effects of androgens on protein metabolism.

Some general tips for balancing your estrogen production include (47 - 50):

  • Eating a balanced diet that includes adequate amounts of vitamins, minerals and fiber
  • Limiting the consumption of soy and phytoestrogens from plant sources
  • Limiting alcohol consumption, as this impairs the liver's ability to metabolize estrogens
  • A regular exercise program
  • Maintaining a healthy body weight, which includes avoiding obesity as well as being severely underweight

Thyroid hormones

Thyroid hormones are a master regulator of metabolic rate and affect nearly every cell in the human body. The thyroid gland produces thyroxine (T4) and triiodothyronine (T3), with T4 being the prohormone of T3. On a molar basis, T3 is about 20 times more potent than T4 and is therefore considered the "true" thyroid hormone (most of the circulating T3 consists of deiodinated T4).

Scientific research seems to suggest that thyroid hormones can increase both body-wide protein synthesis and body-wide protein breakdown, with the latter effects being more pronounced, resulting in a net catabolic effect on total body protein metabolism (51, 52).

In general, thyroid hormones play a fundamental role in the regulation of protein metabolism in normal physiological ranges and it is inappropriate to conclude from data obtained in the context of synthetically induced hyperthyroidism that normal thyroid function is inherently catabolic.

Nor does there appear to be any benefit in terms of skeletal muscle anabolism or whole body protein anabolism from an increase in thyroid hormone production or use of exogenous thyroid hormones - and if there is an effect, it is likely to be catabolic in nature.

Thyroid Hormones Summary:

As the main aim of this article is to examine the effects of these hormones/factors on protein metabolism, the above section does not cover the role that thyroid hormones play in carbohydrate and fat metabolism. It is sufficient for you to know that the catabolic nature of thyroid hormones means that they would have a beneficial effect on fat loss due to the upregulation of metabolic rate (this is also the reason why people who suffer from hyperthyroidism are usually underweight and/or have a hard time gaining weight).

However, if your goal is anabolism (especially of skeletal muscle tissue), then manipulating your thyroid hormone levels doesn't seem wise. This means that the best way to support optimal protein metabolism is to simply maintain normal thyroid function within the normal physiological range.

"Stress hormones" glucocorticoids (primarily cortisol), glucagon and epinephrine

The term "stress hormone" is often used in the scientific literature when referring to glucocorticoids (primarily cortisol), glucagon and catecholamines (more specifically epinephrine/adrenaline). This is primarily due to the fact that the release of these hormones is stimulated in response to stress (in this context it is important to understand that stress does not always have to be a bad thing).

Glucocorticoids are a class of steroid hormones produced in the adrenal glands that regulate metabolism, development, immune function and alertness. The primary glucocorticoid in humans is the stress hormone cortisol. Cortisol is an essential hormone that is necessary for the maintenance of life, but like many other hormones, too high (or too low) levels can have devastating consequences for the body.

Cortisol is often involved in the process of muscle atrophy/degradation as it acts primarily as a catabolic hormone in terms of its metabolic functions. During periods of malnutrition/fasting, cortisol helps to maintain normal blood glucose concentrations by initiating gluconeogenesis. This is often done at the expense of protein degradation in order to use amino acids as substrates for the process of gluconeogenesis.

Glucagon is a peptide hormone produced by the pancreas that basically has the opposite effect of insulin (i.e. it stimulates the release of glucose from the liver into the bloodstream when blood glucose levels fall). Similar to cortisol, glucagon also influences gluconeogenesis and glycogenolysis.

The final hormone in this triad is epinephrine/adrenaline (which is sometimes referred to as the "flight-or-fight" hormone). This hormone is produced by the central nervous system and the adrenal glands and acts in pretty much all tissue types in the body by docking to the adrenoceptors. Just like cortisol and glucagon, epinephrine also stimulates glycogenolysis in the liver and muscles.

Protein synthesis rates in skeletal muscle tissue appear to decrease dramatically in response to stress hormones (53, 54, 55). Prolonged exposure to stress hormones impairs protein synthesis, leading to atrophy of muscle tissue (56).

It is also important to note that epinephrine and cortisol can inhibit insulin secretion - remember that insulin is an anabolic hormone. Some research also suggests that cortisol reduces local synthesis of IGF-1, which would be counterproductive to the goal of protein anabolism (57).

Stress hormones Summary:

The bottom line here is not that stress hormones are some sort of diabolical hormones to be avoided or suppressed at all costs, as this is frankly not what is desirable (in fact, stress hormones are vital in many ways).

The data seems to show that an intake of these hormones promotes protein breakdown and stimulates oxidation of amino acids in most tissue types in the body. They can also impair protein synthesis at chronically elevated levels and reduce insulin secretion and the local release of IGF-1. Ultimately, the accumulation of these actions results in a net catabolic effect.

However, you should not misconstrue this message to mean that acute surges of these hormones (as can be observed during periods of acute stress) are counterproductive to muscle growth, as this would ignore the bigger picture - to reiterate, stress hormones are a necessary part of human physiology. Unless you suffer from abnormally high levels of cortisol, glucagon or epinephrine in the blood over a prolonged period of time (as is the case with Cushing's syndrome, chronic stress, etc.) there is probably no reason to worry about lowering or inhibiting these hormones, as this would be neither beneficial nor healthy.

Let's put it all together

Even though this article is packed with scientific jargon, I hope it has given the reader an understandable overview of some of the primary factors that influence protein metabolism. This is a complex topic and protein metabolism is a growing field of research, which is what makes it so interesting to look at and discuss in more detail.

It is not the intention of this article to advocate the use of any of the compounds or hormones described in the reviews. The options described in this article for modulating the levels of some of these hormones only concern the body's own production and not the administration of exogenous hormones.

Last but not least, remember that many physiological processes are not black or white or on/off switches. It is always crucial that we consider the circumstances and context of the situation. It is neither purposeful nor wise to ignore individual variables that come into play when giving someone advice on nutrition and training.

For this reason, this article is only intended to serve as a broad overview of the factors that influence and/or regulate protein metabolism and to provide you, the reader, with the necessary information to help you make optimal nutritional and lifestyle choices to achieve your individual goals.

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