Thyroid hormone is carried in the blood, bound to proteins, to tissues almost everywhere. Inside cells it binds its receptors and changes which genes are switched on. So its effects are not confined to one organ: a shortage or an excess shows up in many organs at once.
Does one hormone reach every organ, and does it do the same thing at every age?
The hormone reaches almost every cell in the body, but its job depends on the stage of life. Its effects fall into two settings: development before and just after birth, and adult life.
Before and just after birth the body is still being built, and the hormone shapes what gets built: the brain’s cells, their wiring and their insulation, and the growth of the body. Once development is complete, the hormone’s main role shifts to setting the pace of metabolism and the working of individual organs.
Most of the signal is delivered by T3, the active form of the hormone. T3 binds the thyroid hormone receptors more tightly than T4 does, and that is why it carries most of the receptor signal. Tissues make T3 from T4 by conversion.
What does the hormone build before birth?
The brain is one thing it builds. Thyroid hormone is required for normal brain development during fetal and early postnatal life. It drives several steps, and each one builds part of the circuit:
- production of new neurons;
- differentiation of neurons and glial cells;
- migration of neurons and glial cells;
- formation of synapses;
- myelination of nerve fibers.
New neurons are made, become their type, move to the right place, connect by synapses and are wrapped in myelin. The hormone drives each of these steps.
These steps happen in a fixed window. If the hormone supply is inadequate in that window, the brain matures poorly. Thyroid hormone deficiency during fetal and postnatal development is described as causing retarded maturation, intellectual deficits and neurological impairment. The resulting intellectual disability cannot be reversed by treatment started later. The account in the literature is that delay in treatment can lead to irreversible neurological deficits, which fits steps that were missed in their window.
Where does the fetus get the hormone it needs early on?
The brain needs the hormone during its window, so where does the fetus get it before its own gland works? The fetal thyroid gland begins to produce hormone only around the 11th week of gestation. Until then any hormone the fetus needs is supplied from the mother’s reserves. That is why the fetus depends on its mother for thyroid hormone early on.
Does the same hormone build the rest of the body?
It does. The hormone that builds the brain is also required for somatic growth. It acts directly and through growth hormone, and whole-body growth does not occur without it even when growth hormone is adequate. A child lacking thyroid hormone grows poorly.
The hormone also acts on muscle. Using heart muscle as the example, thyroid hormone increases expression of myosin, because it switches on the myosin genes. The muscle then has more of one of the proteins that generate force.
Once the body is built, what does the hormone set?
Growth is finished, so the hormone switches to setting the pace of the body. In adult life it sets the rate at which the body spends energy, and it sets the activity of several organs.
The best-known adult action is on basal metabolic rate. The hormone raises the rate at which cells consume oxygen. One route to this is the sodium-potassium pump: the hormone increases the gene expression of the pump, and the pump’s activity raises basal metabolic rate and oxygen consumption. The same higher rate of work gives off heat, so the hormone also raises the rate at which cells produce heat. The result is that the body spends more energy at rest.
The level of the hormone changes body weight. It also changes tolerance of cold, because heat production is part of what keeps the body warm.
What does that pace do to the heart and the vessels?
The rise in energy and heat shows up in the circulation. The hormone acts directly on the heart. It has an inotropic effect on cardiac muscle cells, increasing the force of contraction, and a chronotropic effect, increasing heart rate.
It also acts directly on arteriolar smooth muscle, which relaxes. The vessels widen, and systemic vascular resistance falls.
Together these changes raise cardiac output. This is the picture seen when the hormone is in excess. When the hormone is deficient, the circulation slows.
What does the hormone do to cholesterol in the liver?
The liver is one more organ whose work the pace sets. In the liver, thyroid hormone changes how lipids are handled. It stimulates lipolysis and it stimulates lipogenesis.
It also lowers circulating cholesterol. The liver’s LDL receptors are controlled by the hormone. The low plasma LDL-cholesterol of hyperthyroidism is linked to more LDL receptor transcription in the liver.
So the lipid profile shifts when the hormone level changes.
What about the nervous system and reproduction?
The brain in adults is affected like the other tissues. Thyroid hormone acts on the nervous system through its receptors, mainly TR-alpha-1 and TR-beta-1. Excess or deficiency of the hormone typically changes mood and alertness. Both too little and too much alter mental state, and mood and cognitive disorders are part of the close link between the nervous system and thyroid function.
Thyroid hormone also influences reproductive function. Normal reproductive behavior and physiology depend on essentially normal levels of the hormone.
Does pregnancy change this system?
Pregnancy changes the thyroid axis itself. What happens to the thyroid axis during pregnancy?