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In today’s post we’ll be talking about some of the more popular hormones out there, namely thyroid hormones, and their effects on the brain.

(This post is part of our series “Hormone Effects on the Brain“)

The thyroid gland

Although you’ll more commonly hear it described as butterfly-shaped, you can think of the thyroid gland as a cute little bowtie which keeps your windpipe warm. The sides of this personalized bowtie are called lobes and they are connected in the middle by a small bridge called the isthmus. Your thyroid is rich both with blood vessels, as well as with tons of little fluid-filled pouches called follicles. In addition, cozily tucked away on the back of your thyroid is another team of great glands: the parathyroids. But we’ll talk more about those in another post. For now, let’s turn our attention to today’s stars, the products of our thyroids.

The thyroid hormones

Structure and production

The thyroid produces three types of hormones:

1. thyroxine or T4 in short (named like this because it contains four iodine atoms)
2. triiodothyronine or T3 (which contains three iodine atoms)
3. calcitonin

The first two are produced inside the follicles. The latter is produced by the so-called parafollicular cells, i.e. the cells surrounding the follicles. Calcitonin has only limited effects in the human body (it’s involved in Ca2+ regulation). That’s why we won’t be focusing on it from here onwards.

T4 and T3, i.e. the most important thyroid hormones, come from an amino acid called tyrosine. The synthesis of each hormone means that two tyrosine molecules come together and join forces with four, respectively three iodine atoms.

Most of the hormones secreted by the thyroid gland are actually T4 hormones, as this is the inactive one. T3, the biologically active between the two, is mostly produced locally, in cells, where some enzymes named deiodinases remove one iodine atom from T4 molecules, thus transforming them into T3.

Regulation of hormone levels

Your thyroid isn’t constantly releasing these hormones into your bloodstream, as that would be quite bad for you. But how does the thyroid know when to release them?

The thyroid is releasing hormones when it receives a signal to do so from its boss, the pituitary gland. This signal is called thyroid stimulating hormone or TSH in short, and it is only released when the pituitary gets the go signal from its own boss, the hypothalamus. You guessed it, this is also a hormone, i.e. thyrotropin-releasing hormone (TRH). The hypothalamus, in turn, can figure out when to start the whole process due to receptors on its surface which respond to thyroid hormones. When the concentration of T3 and T4 in your bloodstream is low, there is a low chance that these hypothalamic receptors are activated. So, in absence of a signal, the hypothalamus starts pumping out TRH. When the T3/T4 concentration finally increases, more and more of these hormones bind to the hypothalamic receptors, shutting down the TRH secretion. Furthermore, thyroid hormones can directly inhibit TSH secretion from the pituitary through the same mechanism. This whole process is a negative feedback loop (i.e., the more you have of something, the less you need to produce).

Effects

Now that we’ve cleared the basics in terms of thyroid hormones, it’s time to turn our attention to what they actually do in the body. And in order to that, we’ll divide their effects into general and brain-related.

General effects

T3 and T4 affect virtually all organs in the body. Generally speaking, they have a stimulating effect. Thyroid hormones increase the heart rate, stimulate the respiratory centers, thus leading to increased oxygenation, and promote development of type II muscle fibers (capable of fast and powerful contractions). Furthermore, they increase your body temperature and speed up your metabolism. Additionally, in children, together with the growth hormones, they also help with bone growth.

Thyroid hormones are also vital for a normal reproductive function, both in males and females. The uterus, ovaries, and placenta have thyroid hormone receptors whose activation leads to a direct effect on the metabolism and growth of these organs. Similarly, testicular cells express thyroid hormone receptors, whose activation stimulates cell proliferation and differentiation. Furthermore, thyroid hormones affect reproductive function indirectly, through interactions with other hormones, such as estrogen and prolactin.

Brain effects

Thyroid hormones affect the brain even before an individual is born. During fetal development, they play a crucial role in the formation of the brain. Studies have shown that they accelerate the myelinating process, control neurogenesis (i.e. the formation of new neurons), as well as regulate synapse formation. If the mother suffers from either hypothyroidism or lacks enough iodine (which is important for thyroid hormone production), it can result in delayed myelination, reduced formation of neurons, as well as fewer synapses in the fetus. On the other hand, hyperthyroidism appears to also result in fewer synapses, but for a different reason. In this case, studies suggest that some types of neurons grow much faster compared to others, which in turn causes them to form fewer synapses with one another.

As you can imagine, these abnormalities in brain structure further translate into cognitive and behavioural impairments. As such, children can end up suffering from a variety of neuropsychological issues, ranging from mild cognitive impairment to schizophrenia.

Throughout the lifespan, thyroid hormones remain crucial for the proper functioning of the nervous system. Although the molecular and cellular mechanisms are less clear when it comes to more complex cognitive functions, the effects of thyroid hormones on the brain in adults become readily apparent when one examines people who suffer either from deficiency or excess of these hormones.

As such, hyperthyroid adults show a lack of concentration, irritability, anxiety issues, depressive symptoms, as well as impaired memory performance. At the neural level, they have decreased functional connectivity in areas associated with attention and cognitive regulation. This could explain at least some of these symptoms.

At the other end of the spectrum, hypothyroidism can lead to tiredness, depression, confusion, as well as learning and memory impairments. The latter seem to occur because the hippocampus, an area of the brain crucial for memory formation, suffers alterations in the absence of proper thyroid function.

Conclusion

As we’ve seen, thyroid hormones affect virtually all organs in the body. They have complex action mechanisms and they can also interact with other hormones. Their role is generally to promote growth and energy consumption. In terms of brain effects, they are crucial both for brain maturation, as well as for maintaining proper cognitive functioning. Too little or too much thyroid hormone secretion leads to serious neurodevelopmental and neuropsychological issues.

What did you think about this post? Are there any specific aspects you’d like us to delve deeper into? Let us know in the comments below.

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References

Banks, W. A. (2012). Brain meets body: the blood-brain barrier as an endocrine interface. Endocrinology, 153(9), 4111-4119.

Chiamolera, M. I., & Wondisford, F. E. (2009). Thyrotropin-releasing hormone and the thyroid hormone feedback mechanism. Endocrinology, 150(3), 1091-1096.

Li, L., Zhi, M., Hou, Z., Zhang, Y., Yue, Y., & Yuan, Y. (2017). Abnormal brain functional connectivity leads to impaired mood and cognition in hyperthyroidism: a resting-state functional MRI study. Oncotarget, 8(4), 6283.

Nicholson, J. L., & Altman, J. (1972). The effects of early hypo-and hyperthyroidism on the development of the rat cerebellar cortex. II. Synaptogenesis in the molecular layer. Brain research, 44(1), 25-36.

Ritchie, M., & Yeap, B. B. (2015). Thyroid hormone: Influences on mood and cognition in adults. Maturitas, 81(2), 266-275.

Rivas, M., & Naranjo, J. R. (2007). Thyroid hormones, learning and memory. Genes, Brain and Behavior, 6, 40-44.

Shahid, M. A., Ashraf, M. A., & Sharma, S. (2018). Physiology, thyroid hormone.

Silva, J. F., Ocarino, N. M., & Serakides, R. (2018). Thyroid hormones and female reproduction. Biology of reproduction, 99(5), 907-921.