The Wonders of Your Liver

Being one of the largest organs in the body, the adult liver weighs approximately three pounds. On average, it comprises about 2% of the average weight of an adult, but don’t let its size fool you.

The liver has many vital metabolic functions. Although it is most associated with detoxification, a process that helps our body convert toxic substances into harmless compounds to be excreted, it does so much more.

One connection that is often overlooked is the role our liver has on hormonal regulation and vice versa. Hormones influence liver processes, and the liver impacts hormones in various ways.

In this article, we’ll explore all the wonders of our liver and this liver-hormone link.

Topics include:

• How the liver affects overall health
• The main functions of the liver
• How hormones impact the liver
• How the liver regulates hormones
• The liver-gut-thyroid connections
• The group of bacteria in the gut that metabolize estrogens and their relationship with the liver
• A summary on the liver-hormone link

After reading it, you’ll understand why I almost always include some form of liver support with all my clients, especially those with hormonal issues.

This post will prime you for my follow up article. In it, I’ll discuss hormonal imbalances and how functional medicine strategies to test and optimize the liver can help to re-harmonize them.

Let’s get started!

How Does the Liver Affect Overall Health?

Almost every organ system is influenced by the liver. For example, the liver:

• impacts the endocrine (hormonal) system by playing a role in hormone levels
• aids digestion and is a storage location for nutrients
• regulates cholesterol, which is the precursor to hormones and impacts lipid levels
• influences the cardiovascular system through production of various proteins and processing red blood cells
• plays an important role in the body’s immune response (via its Kupffer cells and Pit cells)

The Functions of the Liver

The liver’s influence on our physiology is vast. In fact, it has been estimated to have over 500 essential functions!

Some of the most well-known functions of the liver include:

• Production of bile for removal of waste and breaking down fats in the small intestine
• Synthesizing certain blood plasma proteins, including albumin which carries hormones, vitamins, and enzymes throughout the body and helps maintain our fluid balance
• Production of cholesterol and special proteins that transport fat throughout the body
• Synthesis of glycogen from excess glucose, which helps to balance out blood sugar (glycogen can then be broken down into glucose when needed for energy)
• Regulation of amino acids, the building blocks of proteins
• Storage of fat-soluble vitamins and minerals (iron and copper)
• Metabolizing poisonous ammonia to form urea, an end product of protein metabolism
• Cleansing the blood of drugs, chemicals, and dangerous substances
• Regulating blood thickness and clotting factors
• Production of immune factors and removing bacteria from the bloodstream
• Bilirubin conjugation, in which this metabolite from red blood cells is joined with glucuronic acid to allow it to be carried in bile and excreted
• Acting as a site for thyroid hormone function, removing an iodine from the inactive form of thyroid hormone (T4) to produce the active form (T3)
• Removal of wastes: After the liver has broken down harmful substances, its metabolites are transported into the bile or blood.
  • The by-products in bile are carried into the intestine and exit the body in the form of feces.
  • The kidneys filter out break-down products in the blood and excrete them through the urine.

To summarize, the liver regulates most chemicals in the body and processes all the blood leaving the stomach and intestines. It breaks down, balances, stores, and creates nutrients, and it expels bile to carry away waste. It also metabolizes drugs and harmful compounds into non-toxic byproducts.

Now that we have an overview of all the vital processes the liver is involved with, let’s narrow our focus to how it’s linked to hormones.

How Hormones Impact the Liver

The endocrine system and the liver are tightly interwoven. Hormones act on the liver regulating its metabolic processes and protein synthesis. These complex interactions occur through receptors found in the liver. Hormonal actions to mediate the liver’s responses are dependent on the presence of these specific receptors and their concentrations.

For example, both endogenous and external sources of estrogen have been found to alter the production of several liver proteins, such as hormone and mineral transport proteins, some drug-metabolizing enzymes, and others. Furthermore, there is evidence that estrogens and androgens support liver cell regeneration.

How Does the Liver Affect Hormones?

As highlighted already, the liver plays a key role in hormone modulation. More specifically, this includes:

1. Transforming inactive hormones to active compounds (e.g., Thyroid hormones: thyroxine (T4) into triiodothyronine (T3), Vitamin D: vitamin D3 into 25-hydroxy (25-OH) vitamin D).
2. Inactivating, metabolizing, and excreting hormones from the body.
3. Synthesizing transport proteins which regulate hormone levels. (When hormones are bound for transport, they remain inactive until they get to their target tissue.)
4. Production of hormone-dependent growth factors and inhibitors.

For this reason, pathologies and damage to the liver, such as non-alcoholic fatty liver disease (NAFLD), can affect endocrine functions, and vice versa.

The Liver-Gut-Thyroid Connection

Another way the liver and hormones are connected are through the liver’s interactions with the gut and thyroid. Specifically, there is a liver-gut axis and a gut-thyroid link.

The Liver-Gut Connection

The portal vein (a blood vessel that carries blood from the gastrointestinal tract, gallbladder, pancreas, and spleen to the liver) is the bi-directional connecting link between the gut and the liver. It delivers metabolites made in the intestines to the liver. These break-down products stimulate the liver to produce bile and antibodies. The cycle continues when bile and these immune substances are then secreted back into the digestive tract where they can be further metabolized by its microbes.

This feedback loop between the gut and liver is called enterohepatic circulation, and it determines the amount of bile acids produced, which is vital for proper detoxification of the body. This process regulates the excretion of neutralized substances, including hormones, and assists with fat digestion.

The Role of the Liver-Gut Link in Estrogen Clearance

The liver’s ability to inactivate, metabolize, and excrete hormones from the body is tightly interwoven with its interaction with the gut and the special microbial population it hosts.

The Estrobolome

There is a specific group of bacteria that exist in the gastrointestinal tract that are capable of metabolizing estrogens. These microbes are collectively called the estrobolome.

The bacterial species in the estrobolome possess B-glucuronidase (GUS) enzyme activity. These enzymes recycle estrogen back into the blood instead of being eliminated through the stool.

In general, the more of these microbes that are present, the less estrogen is eliminated. If there is dysbiosis, an imbalance of the gut microbiota, estrogen levels can be disrupted even more. This can result in hormonal imbalances, inflammatory estrogen metabolites that are not eliminated, and estrogen dominance. Estrogen dominance (a greater ratio of estrogen to progesterone and other sex hormones) is linked to biological female health disorders (e.g., endometriosis, polycystic ovary syndrome, and fertility issues).

The Liver-Thyroid Axis

The liver and thyroid’s bidirectional relationship is similarly as complex as its interplay with the gut. The liver regulates thyroid hormone activation, inactivation, transport, and breakdown. Thyroid hormones, conversely, impact liver metabolism and processes.

The liver precisely influences thyroid function in the following ways:

1. Hormone activation and inactivation:

• The liver is responsible for the production of 30-40% of active thyroid hormone, T3 (via the presence of the type 1 deiodinase enzyme).
• It also catalyzes the conversion of other thyroid hormone subtypes by cleaving off iodine at various positions including T4 to rT3 (reverse T3, an inactive form of T3 often resulting from infections), T3 to T2, and rT3 to rT2.20.

2. Transport and metabolism:

• The liver extracts 5–10% of T4 out of our blood plasma through a specific transport mechanism within the liver cells.
• The liver also synthesizes several plasma proteins that bind thyroid hormones. Over 99% of thyroid hormones are bound to various proteins (i.e., thyroxine-binding globulin, thyroxine-binding prealbumin, and albumin in plasma) which provides a pool of circulating, inactive hormones.

This relationship between the thyroid and liver has been shown clinically. Serum liver enzyme abnormalities, indicating impaired liver function, have been found in patients with hypothyroidism and hyperthyroidism. Furthermore, those with various liver diseases are at risk for hypothyroidism for the above-mentioned reasons.

Summary: The Liver and Hormones

The liver is a key organ for a variety of body processes. There is a complex, bi-directional relationship in which the liver regulates and metabolizes hormones, and hormones also influence liver function. Within this interaction, the gut microbiome also has an impact in recycling hormones through its connection to the liver.

In summary, the liver plays a role in hormonal levels in the following ways:

(1) it makes proteins that hormones use to travel throughout the body, which effects their availability for cellular uptake

(2) it interacts with estrogen through the estrobolome

(3) it is the major site of hormone metabolism

(4) it converts thyroid and other hormones into their active forms

(5) it influences many other processes in the body that impact hormone levels

Do you now have a new appreciation and love for your liver?

In the follow up post, we will review more of what occurs when hormones are imbalanced and how lifestyle practices, nutrients, supplements, and herbs can be used to optimize liver health and function. This, in turn, will support hormonal health and overall vitality.

Stay tuned to learn how to better care for your liver and your hormones.

Naturopathic Medicine and Holistic Resources for Hormonal, Mood, and Digestive Support

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