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Is Thyroxine a hormone?

Is Thyroxine a hormone?



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I have read the phrase 'T3 is three to four times more potent than T4' several times both in books and websites. But isn't T4 a prohormone of T3? Why do then these sources talk about its potency as a hormone(I suppose)?


It is necessary to distinguish between classical and non-classical actions of thyroid hormones.

Classical action involves nuclear THR (or TR) receptors (TR alpha1, TR beta1, TR beta2). They are activated by T3, 3,5-T2, TRIAC and 3,5-DIAC, and blocked by rT3 and rTRIAC. T4 and TETRAC hardly have an effect on nuclear thyroid hormone receptors, but they are converted in the periphery and in target tissues by deiodinases to T3 and 3,5-T2, and TRIAC and 3,5-DIAC, respectively. From the classical perspective, T4 and TETRAC are therefore prohormones and not hormones in the narrower sense.

Non-classical action denotes binding of thyroid hormones to integrin receptors on the cell membrane. The resulting non-genomic actions may be directly mediated by T4 and TETRAC and don't require deiodination. From the non-classical perspective T4 and TETRAC are hormones sensu stricto.

Figure from Hoermann et al. 2015 (CC BY license)

References

  1. Hoermann R, Midgley JE, Larisch R, Dietrich JW. Homeostatic Control of the Thyroid-Pituitary Axis: Perspectives for Diagnosis and Treatment. Front Endocrinol (Lausanne). 2015 Nov 20;6:177. doi: 10.3389/fendo.2015.00177. eCollection 2015. Review. PMID 26635726

  2. Davis PJ, Goglia F, Leonard JL. Nongenomic actions of thyroid hormone. Nat Rev Endocrinol. 2016 Feb;12(2):111-21. doi: 10.1038/nrendo.2015.205. PMID 26668118.


Both T3 and T4 are functional in human body… T3 being only more potent. Both of them fulfill the features of being a hormone, in fact both of them serve the same function in human body. Yes, T4 produces T3 in the peripheral circulation, so you can say it is a pro-hormone of T3, but that dosen't remove it from the hormones. Another example is Angiotensin I which is a pro-hormone (besides itself being a hormone) of Angiotensin II. There are so many other examples.

Following are the references for my answer - Ganong W F, Review of Medical Physiology, 25th edition, 2016, page- 341 http://press.endocrine.org/doi/abs/10.1210/jcem-36-6-1050?journalCode=jcem https://www.labome.org/grant/r21/hd/is/thyroxine/is-thyroxine-more-than-a-prohormone--8448119.html http://thirdworld.nl/l-thyroxine-acts-as-a-hormone-as-well-as-a-prohormone-at-the-cell-membrane


I don't know, but I suspect that T4 was characterized first and fulfils the classic definition of a hormone being secreted by a gland and carried in the blood to its target.

Potency is the measure of some biological or biochemical assay of the effect of these agents in the target tissue, so that you can talk about potency regardless of other attributes of a molecule.

Even when it was established later (I presume) that T4 is converted to T3 in the target tissue, and T3 is very active, the possibility would have existed that this conversion might only be partial (there will presumably always be some T4 present there) and the question arises whether both of these molecules have biological activity and function. The results of measurements of 'potency' are part of the argument or consideration as to whether T4 is just a precursor or also an agent in its own right.

I think the thing to bear in mind is although you might read nice clear-cut statements in text books and the like, the observations on which they are based are often not so clear-cut, so authors are being both prudent and scientific in presenting the data to the reader.

Finally, there is the question of semantics. Even if T4 is completely converted to T3 in the target tissue, you could still say that it is a hormone because it is secreted by an endocrine gland, passes in the blood to a target tissue where it has an effect. The fact that its effect requires it to be modified in the tissue doesn't invalidate its description as a molecule that has an effect on a target tissue. So on that basis you can justify calling it a hormone (as well as a prohormone). I also suspect there may be historical reasons for retaining the description.


Both T3 and T4 are hormones produced by thyroid. The difference between the two is the presence of 3 reps. 4 iodine atoms. Hormones usually work only on specific cells, by interactions to specific receptors. These receptors may be found on cellular membrane, intracellular, on nuclear membrane or even inside the nucleus. So, to answer your question, T3 is more potent with reference to T4 hormone for the fact that only T3 can enter the nucleus of the cell. Therefore T4 must be reduced to T3 to generate a nuclear answer.

Lang, Schmidt, Heckman, "Physiologie des Menschen", 31.Auflage


Thyroxine

Definition
noun, plural: thyroxines
An iodine-containing hormone (chemical formula: C15H11I4NO4) produced by the thyroid gland to regulate metabolism by controlling the rateof oxidation in cells
Supplement
In animals, hormones are substances produced and secreted by an endocrine gland, the ductless gland of the endocrine system. In humans and other vertebrates, the thyroxine is a hormone produced and secreted by the follicular cells (thyrocytes) of the thyroid gland of the endocrine system. In humans, the thyroid gland releases two types of thyroid hormones: (1) thyroxine and (2) triiodothyronine.
In humans, thyroxine is a thyroid hormone involved in the regulation of metabolism and the control of growth. Similar to triiodothyronine, thyroxine is tyrosine-based and has iodine as a structural component. Thyroxine is 65% iodine. Thus, a deficiency of iodine could hamper the production of these hormones, and manifest as a disease called simple goiter.
Thyroxines are released into the bloodstream and most of them are bound to proteins (e.g. thyroxine-binding globulin, transthyretin, albumin, etc.). Thyroxines are more predominant and have a longer half-life than triiodothyronines. Nonetheless, triiodothyronines are more potent than thyroxines. These thyroid hormones target nearly all cells of the body. Thyroxines cross the cell membrane via ATP-dependent carrier-mediated transport. Within the cell, thyroxine is converted into the active triiodothyronine by deiodinase enzyme. It is further processed to produce iodothyronamine and thyronamine. The triiodothyronine binds to the nuclear receptor, thyroid hormone receptor. The binding causes conformational change in the receptor, displacing the corepressor molecules. The corepressor together with the receptor binds DNA regions called thyroid hormone response elements near genes. The complex blocks the transcription of certain genes. Thus, the displacement of corepressor from the complex leads to the recruitment of coactivator proteins and RNA polymerase, and the subsequent activation of gene transcription.
Thyroxines and triiodothyronines are involved in augmenting basal metabolic rate. They are also involved in the regulation of protein, fat, and carbohydrate metabolism. They are also involved in stimulating vitamin metabolism. In other animals, such as mammals, they are involved in hibernation cycles. In birds, they are associated with the moulting behavior.
The thyroid stimulating hormone (TSH) targets the pituitary gland to release thyroxine. Negative feedback occurs when thyroxine levels in the body are high, as this inhibits the secretion of TSH.
Thyroxines may be synthetically produced for use as a medication in treating hypothyroidism.
Chemical formula:

  • hormone
  • thyroid stimulating hormone

Last updated on March 1st, 2021


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In the Body, What Is the Role of Thyroxine? (with pictures)

Thyroxine is one of the main hormones secreted from the thyroid follicular cells. Within the body, thyroxine affects the body’s metabolism and has an effect on protein synthesis. It is also important for human growth and development, as it regulates bone growth and aids in the maturation of neurons. This hormone also increases the catecholamine effect, the body’s sensitivity to adrenaline. There are health issues linked to low and high levels of this hormone in the body.

Thyroxine is also known as T4, as the molecular structure consists of thyronine molecule with four iodine molecules. Synthesis occurs in the thyroid gland. The hormone is released into the blood through the thyroid follicular cells. Approximately 80 percent of all T4 is produced in the follicular cells.

In the body, T4 is transported to cells via the blood. Only free or unbound hormones are passed into cells and considered active. Up to 99 percent of thyroxine is actually bound to proteins in the blood. An individual’s concentration of free T4 in the blood is extremely important in medical investigation and diagnosis.

This particular hormone influences metabolism by regulating how much oxygen the cells use, and by creating body heat. Within the liver, T4 directly affects cellular respiration, the process of transforming glucose and oxygen into energy and carbon dioxide. The presence of thyroxine promotes the first step of metabolism, going from glucose to pyruvate. Within the stomach and intestines, T4 promotes muscle contraction and digestive juice secretion.

As children age, T4 is responsible for regulation of growth and development. The hormone coordinates bone growth with age, as well as development of cardiac and skeletal muscles. In the skin, T4 is responsible for hair growth. As children mature, the presence of the hormone results in breast milk production and the ability to conceive. During developmental years, T4 also is responsible for normal development of nerves and neurons.

The catecholamine effect refers to the body’s response to stress, invoking the flight or fight response in the body. This response is due to the presence of adrenaline and noradrenaline in the body. The presence of thyroxine increases the body’s sensitivity to catecholamine compounds.

An overactive or underactive thyroid can result in issues with T4 levels in the body. Too much T4, due to hyperthyroidism, results in nervousness, weight loss, and other potentially serious health issues. An under-active thyroid can result in a number of other health conditions, including developmental problems and weight gain. Supplements may be used to increase the level of thyroxine in the body. Overactive thyroids are sometimes destroyed or removed and hormone therapy used to provide the necessary hormones for proper body function.


Is Thyroxine a hormone? - Biology

Thyroxine, or 3,5,3',5'-tetra­iodothyronine, a form of thyroid hormones is the major hormone secreted by the follicular cells of the thyroid gland. Thyroxine is synthesized via the iodination and covalent bonding of the phenyl portions of tyrosine residues found in an.
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thyroxine also thyroxin n. An iodine-containing hormone, C 15 H 11 I 4 NO 4 , produced by the thyroid gland, that increases the rate of cell
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Thyroxine Thyroxine IUPAC name (2 S )-2-amino-3-[4-(4-hydroxy -3,5-diiodophenoxy)-3,5-diiodo phenyl]propanoic acid Identifiers CAS number
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Function of Thyroid Hormone

Thyroxine (T4) and Triiodothyronin (T3) are the two thyroid hormones. These two hormones have the same functions. Although T3 is more potent, T4 is considered as the chief hormone of thyroid, because the latter is secreted many times more than the former quantitatively. For our discussion about the function of hormone, the actions of T4 and T3 in the body are as follows:--

Metabolic actions

BMR and calorigenesis

T3 and T4 increase the BMR by stimulating oxidation of foodstuff in the tissues and therefore these hormones are also called calorigenic hormones. During cold, the secretion of thyroid hormones is increased, which by stimulating calorigenesis help in thermoregulation and avoid fall of body temperature.

Metabolism of Carbohydrate

Another function of thyroid hormone is to raise the blood sugar level by increasing food intake, absorption of glucose from intestine, glycogenolysis, neoglucogenesis etc. These hormones also increase the oxidation of glucose in tissues as well.

Metabolism of Protein

Under normal conditions that means, when the blood levels of T4 and T3 are within normal range, these hormones help in protein synthesis but when secreted in excess, they cause protein breakdown.

Metabolism of Fat

T3 and T4 stimulate the catabolism of fat by activating the enzyme lipase present in the tissues.

Growth and differentiation

Another function of thyroid hormone is the growth and differentiation. Thyroid hormones help in growth by acting jointly with STH. STH directly acts on tissues to stimulate their growth. T4 and T3 stimulate differentiation of tissues, which indirectly helps in growth by facilitating the action of STH. Requirement of thyroid hormones in metamorphosis of amphibians and molting of reptiles, birds etc., are good examples of developmental effect of these hormones.

Action on nervous system

These hormones help in the development of nervous system and mental functions as evidenced by the fact that in deficiency of these hormones, the subject becomes mentally retarded.

Action on circulatory system

As the function of thyroid hormone its action on circulatory system is also to be noted. Thyroid hormones increase absorption of vitamin B12 from the intestine, which is required for synthesis of hemoglobin and thereby erythropoiesis (i.e.,formation of RBC). T4 and T3 increase the activity of heart.

Action on reproductive system

These hormones help in the growth, development and function of reproductive system. This is most likely due to the stimulatory effect of T4 and T3 on pituitary GTH secretion.

Action on digestive system

Function of thyroid hormone on digestive system is promote hunger, appetite, movement of gastro-intestinal tract and absorption of various materials from the intestine

Hypo- and hyper-secretion of T4 and T3

For details about hypo and hyper secretion of T4 and T3, that means hypo-thyroidism or hyper-thyroidism , as well as the thyroid related diseases please click here:
→ Diseases of Thyroid dysfunction


Hormones help to regulate metabolic processes in the body. Hormones are secreted into the blood through endocrine glands

They travel in the blood to organs where they take effect. The diagram below shows the endocrine system

Hormone Reference Chart

Gland Hormone Target organs Effect
adrenal gland adrenalin vital organs, eg liver and heart Prepares body for action - 'fight or flight'.
ovary oestrogen ovaries, uterus, pituitary gland Controls puberty and the menstrual cycle in females stimulates production of LH and suppresses the production of FSH in the pituitary gland.
ovary progesterone uterus Maintains the lining of the womb - suppresses FSH production in the pituitary gland.
pancreas insulin liver Controls blood sugar levels.
pituitary gland anti-diuretic hormone (ADH) kidney Controls blood water level by triggering uptake of water in kidneys.
pituitary gland follicle stimulating hormone (FSH) ovaries Triggers egg ripening and oestrogen production in ovaries.
pituitary gland luteinising hormone (LH) ovaries Triggers egg release and progesterone production in ovaries.
testes testosterone male reproductive organs Controls

This video explains more about Hormones and the effects they have

Example: The Menstrual Cycle

The menstrual cycle is a recurring cycle of physiological changes in women associated with reproductive fertility.

Four hormones are involved: Oestrogen, Progesterone, FSH (Follicle stimulating hormone ) and LH (Luteinising hormone )

1. The egg ripens in the ovaries - stimulated by FSH

2. Womb lining builds-up - stimulated by Oestrogen

3. Egg is releases - stimulated by the LH (about day 14)

4. Maintenance of uterus lining - stimulated by progesterone

5. Uterus lining breaks down - caused by low levels of oestrogen and progesterone


Human Endocrine System

The human endocrine system is composed of endocrine glands.

  • An endocrine gland is an organ that secretes a hormone directly into the bloodstream.
  • A hormone is a chemical messenger secreted by an endocrine gland directly into the bloodstream where it travels to a target organ/tissue where it exerts a specific effect.

The locations of the various endocrine glands are shown below:

Exocrine versus endocrine glands:

  • Exocrine gland is an organ that secretes its product into a duct.
  • Endocrine gland secretes its product directly into the bloodstream.

Endocrine action versus nerve action:

  • Endocrine action is slow, prolonged, and chemical in nature.
  • Nerve action is fast, short-lived, and electrical in nature.

Endocrine glands

The locations of the three main endocrine glands in the human brain

Hypothalamus:

The hypothalamus is located towards the base of the brain just above the pituitary gland. It secretes hormones directly into the bloodstream that travel the short distance to the pituitary gland and therefore can regulate the secretions of the pituitary, e.g. growth hormone releasing hormone – which causes the release of GH from the pituitary.

Pineal gland:

The pineal gland is located deep within the centre of the brain and secretes melatonin which regulates biorhythms such as sleep and the menstrual cycle.

Pituitary gland:

The pituitary (master endocrine gland) is located at the base of the brain and controls all other endocrine glands (outside of the central nervous system). It secretes many hormones e.g. growth hormone (GH) stimulates protein synthesis and bone elongation (growth).

Giganitism is a symptom of excess secretion of growth hormone and is usually caused by a pituitary tumour which can be treated by surgery, if caught early.

Dwarfism is a symptom of growth hormone deficiency. It is treated by injections of growth hormone during childhood.

Robert Pershing Wadlow suffered gigantism

Thymus gland:

The thymus gland is located just in front of the heart and behind the sternum. It secretes thymosin which helps white blood cells (that are made in the bone marrow) to mature into active immune cells.

Pancreas endocrine gland:

The pancreas is located underneath the stomach on the left hand side of the abdomen.

The pancreas (in yellow)

It is both an endocrine gland and an exocrine gland. The endocrine part is composed of islets of Langerhans which secrete insulin. Insulin enters the bloodstream directly and stimulates all cells in the body to absorb glucose. The exocrine part of the pancreas is discussed in Chapter 33: The Human Digestive System

Symptoms of insulin deficiency and its treatment:

  • Diabetes results if there is no insulin or lack of insulin in the body
  • Insulin is used as a hormone supplement to treat type I diabetes

Adrenal glands:

The adrenal glands are located on top of each kidney in the back of the abdomen. They secrete adrenaline (‘fight or flight’ hormone) which is secreted in times of stress or danger.

The location of the adrenal glands (in yellow)

Functions of adrenaline:

  • Increases blood flow to the brain and muscles
  • Decreases blood flow to the skin and internal organs such as the intestines and kidneys
  • Dilates the bronchioles allowing more air in
  • Increases blood glucose levels
  • Increases heart rate

Ovaries and testes:

  • Ovaries: secrete oestrogen (stimulates changes that occur at puberty in females) and progesterone which are both involved in the menstrual cycle and in preparing the female body for a possible conception
  • Testes: secrete testosterone which stimulates the changes that occur in the male at puberty and also help to maintain these changes (called secondary sexual characteristics)

Anabolic steroids act in the same way in which testosterone acts – builds up muscle – therefore, anabolic steroids are used by body-builders and they have also been used (illegally) by athletes to boost athletic performance


Thyroid Replacement Medicine

Fluctuations in thyroid levels and metabolism can be controlled with medications. By restoring normal metabolic activity from hypothyroidism or Graves' disease, with the use of thyroxine supplementation, body weight can be controlled for most people and BMR can be returned to its optimal levels. This hormone is designed to be used medically under the care of a doctor and is only available by prescription. If you think your metabolism is not normal and that thyroid tests may indicate an imbalance, see a doctor.