Hormones are perhaps the most important messengers in the body. In the case of thyroid hormones, they relay information critical to numerous cells and tissues belonging to multiple bodily systems. However, without the assistance of deiodinases, thyroid hormones are ineffective and remain in an almost unusable state.
The importance of deiodinases should not be overlooked. Having a greater understanding of what they are, their function, and what can inhibit their efficacy allows you to better comprehend your thyroid health.
Introduction to Deiodinases
Deiodinase enzymes are a critical component of proper cellular thyroid function. There are three types of deiodinases: Type 1 Deiodinase (D1), Type 2 Deiodinase (D2) and Type 3 Deiodinase (D3). These powerful enzymes control intracellular activity of thyroid hormones.
Each enzyme is located in various tissues throughout the body with different levels of concentration. For example, D2 is primarily found within the pituitary gland while D3 has no presence there.
The responsibilities and functions of each deiodinase have a common theme of regulating hormone functionality. They accomplish this task by removing iodine from the inactive form of thyroid hormone (known as thyroxine or T4). Depending on the enzyme, the result is an output of active thyroid hormone, triiodothyronine (T3), or reverse triiodothyronine (RT3). These two hormones regulate cellular metabolism. T3 causes an increase of cellular activity while RT3 reduces it.
Because deiodinases are involved in the production and balance of thyroid hormones they have a great deal of control over cellular activation and deactivation.
Individual Qualities of Deiodinases
As mentioned above, there are three different deiodinases, which perform different functions. D1 and D2 convert T4 into T3 whereas D3 converts T4 into RT3. The individual impact of these enzymes on hormone function, and subsequently overall cellular activity, is important.
D1: Type 1 Deiodinase
Type 1 Deiodinase influences non-pituitary regions of the body by converting T4 into T3. This effectively increases cellular activity and keeps tissues and other systems energized. D1 has a minor representative factor in the pituitary but does little to impact overall levels in the gland. Even though D1 aids in the prominence of T3, it is not the primary contributor.
D2: Type 2 Deiodinase
Type 2 Deiodinase also regulates cellular thyroid activity by converting T4 into T3 and is estimated to be 1000 times more efficient than D1.
As the primary contributor of T3 in the pituitary, D2 dictates the degree of cellular activity. The pituitary gland houses a significant amount of active thyroid hormone. Approximately 80-90 percent of T4 in the pituitary is converted to T3 whereas only 30-50 percent of T4 found in peripheral tissues is converted to T3. The notable difference in these numbers is due to the impressive efficiency of D2 within the pituitary in contrast to the relative sluggishness of D1 and the presence of D3 in non-pituitary tissues.
D2 accounts for nearly 80 percent of extrathyroidal T3. This makes D2 the primary facilitator of T3 throughout the body. While D1 is negatively impacted by multiple physiological and emotional stressors, D2 has the opposite response resulting in an increase of T4 to T3 conversion within the pituitary. Because of its significant impact on pituitary hormone levels, the result of various stressors is a pituitary level of T3 that appears normal even though the rest of the body may be suffering from a T3 deficiency.
D3: Type 3 Deiodinase
In contrast to D1 and D2, Type 3 Deiodinase reduces cellular thyroid activity by converting T4 into RT3. This hormone is an important component of thyroid function and is used it block T3 receptors and limit the effect of T3. Reverse T3 also slows metabolism, suppresses D1’s conversion of T4 to T3 and limits cellular uptake of T4 and T3.
D3 is present in every tissue excluding the pituitary. Therefore, an increase in D3 activity does not impede thyroid levels in the pituitary but reduces T3 levels and function elsewhere. This may sound problematic. However, when functioning properly Reverse T3 and D3 help manage hormone levels and properly regulate cellular metabolism.
How Deiodinases Disruption Harms Health
When working as intended, deiodinases harmoniously orchestrate cellular thyroid levels and keep the body working as intended. However, there are multiple factors that can interrupt proper enzymatic function resulting in poor thyroid hormone interaction. This can cause conditions such as hypothyroidism and hyperthyroidism.
Some of the leading causes of deiodinases dysfunction include:
- Chronic dieting
- Chronic pain
- Environmental toxins
- Excessive exercise
- Growth hormone deficiency
- Hormone imbalances
- Insulin resistance
- Leptin resistance
- Major surgery
- Nutrient deficiencies
- Reduced testosterone
- Stress (physiological or emotional)
- Unique deiodinase variations
Of this list of contributors, there are multiple worth investigating further.
Depending on the causal factor, each of the three deiodinases will respond differently. In the event that D1 and D2 are hindered, the conversion of T4 to T3 will be inhibited, whereas a downregulation of D3 results in poor conversion of T4 to RT3.
Stress inhibits D1 activity while increasing D3 activity. The result is an increase of Reverse T3 conversion and a reduction in T3. This causes tissue thyroid levels of T3 to decrease everywhere except in the pituitary. Elevated T3 in the pituitary is triggered by stress and prompts D2 to convert more T4 into T3 within the pituitary. Furthermore, stress impedes immune function, which also contributes to reduced T3 tissue levels.
Depression can contribute to reduced D1 function and lowered cellular uptake of T4. This means that the cell has less T4 to convert to T3 resulting in a T3 deficit. Conversely, D3 function becomes upregulated during depressive states resulting in elevated Reverse T3 levels and limited thyroid hormone receptivity outside of the pituitary.
Unhealthy and chronic dieting can significantly inhibit intracellular and circulating T3 levels. Patients who aggressively diet may experience reduced T3 levels of up to 50 percent. This results in a reduced basal metabolic rate which makes losing weight even more difficult.
Furthermore, the effect of chronic dieting, involving a long-lasting starvation state and lower BMR, can remain for years. This results in patients suffering from decreased T3 levels for extended periods.
Depending on the person, tissue levels of D1, D2, and D3 will vary throughout the body. Different physiological states may result in unique reactions and deiodinases activity. With variance of deiodinases comes variation of T3 tissue levels, which is a key component of symptom intensity related to thyroid dysfunction. Therefore, thyroid-related symptoms present themselves differently in each person.
Uterine and fetoplacental D3 activity increases significantly during pregnancy and may result in the mother requiring hormone supplementation. The increased D3 action reduces T3 prevalence meaning that additional T4, T3, or a combination may be needed to resolve the imbalance. This scenario is significantly more likely if the patient has hypothyroidism.
Digging Deeper with Deiodinases
For those already familiar with thyroid conditions such as hypothyroidism and hyperthyroidism it may come as a surprise that there is more to consider than simple production of T4. Because the enzymes discussed in this article are integral for the production and regulation of T3 and Reverse T3, the thyroid cannot work properly without them.
Malfunctioning deiodinases can inhibit conversion, transport, and receptivity of thyroid hormones. Therefore, it is critical that anyone with concerns of thyroid wellness be well-informed of the significant impact of deiodinases on thyroid function.