Thyrotropin-releasing hormone (TRH) is a hypophysiotropic hormone produced by neurons in the

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus ...

that stimulates the release of

thyroid-stimulating hormone Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism o ...

(TSH) and

prolactin Prolactin (PRL), also known as lactotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secreted from the p ...

from the

anterior pituitary A major organ of the endocrine system, the anterior pituitary (also called the adenohypophysis or pars anterior) is the glandular, anterior lobe that together with the posterior lobe (posterior pituitary, or the neurohypophysis) makes up the pi ...

. TRH has been used clinically for the treatment of

spinocerebellar degeneration Spinocerebellar ataxia (SCA) is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a neurological condition in its own right. An estimated 150,000 people in the United States have a diagnosis of sp ...

and disturbance of consciousness in humans. Its

pharmaceutical A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and ...

form is called protirelin (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...

) ().

Synthesis and release

TRH is synthesized within parvocellular neurons of the

paraventricular nucleus The paraventricular nucleus (PVN, PVA, or PVH) is a nucleus in the hypothalamus. Anatomically, it is adjacent to the third ventricle and many of its neurons project to the posterior pituitary. These projecting neurons secrete oxytocin and a smaller ...

of the hypothalamus. It is translated as a 242-amino acid precursor polypeptide that contains 6 copies of the sequence -Gln-His-Pro-Gly-, flanked by Lys-Arg or Arg-Arg sequences. To produce the mature form, a series of enzymes are required. First, a protease cleaves to the C-terminal side of the flanking Lys-Arg or Arg-Arg. Second, a carboxypeptidase removes the Lys/Arg residues leaving Gly as the C-terminal residue. Then, this Gly is converted into an amide residue by a series of enzymes collectively known as peptidylglycine-alpha-amidating monooxygenase. Concurrently with these processing steps, the N-terminal Gln (

glutamine Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral, ...

) is converted into pyroglutamate (a cyclic residue). These multiple steps produce 6 copies of the mature TRH molecule per precursor molecule for human TRH (5 for mouse TRH). TRH synthesizing neurons of the paraventricular nucleus project to the medial portion of the external layer of the median eminence. Following secretion at the

median eminence The median eminence, part of the inferior boundary of the hypothalamus in the brain, is attached to the infundibulum. The median eminence is a small swelling on the tuber cinereum, posterior to and atop the pituitary stalk; it lies in the area ro ...

, TRH travels to the

via the

hypophyseal portal system The hypophyseal portal system is a system of blood vessels in the microcirculation at the base of the brain, connecting the hypothalamus with the anterior pituitary. Its main function is to quickly transport and exchange hormones between the h ...

where it binds to the TRH receptor stimulating the release of

from

thyrotrope Thyrotropes (also called thyrotrophs) are endocrine cells in the anterior pituitary which produce thyroid stimulating hormone (TSH) in response to thyrotropin releasing hormone (TRH).Guyton, A.C. & Hall, J.E. (2006) ''Textbook of Medical Physiology ...

s and

from lactotropes. The half-life of TRH in the blood is approximately 6 minutes.

Structure

TRH is a tripeptide, with an amino acid sequence of pyroglutamyl-histidyl-proline amide.

History

The structure of TRH was first determined, and the hormone synthesized, by

Roger Guillemin Roger Charles Louis Guillemin (born January 11, 1924) is a French-American neuroscientist. He received the National Medal of Science in 1976, and the Nobel prize for medicine in 1977 for his work on neurohormones, sharing the prize that year w ...

and Andrew V. Schally in 1969. Both parties insisted their labs determined the sequence first: Schally first suggested the possibility in 1966, but abandoned it after Guillemin proposed TRH was not actually a peptide. Guillemin's chemist began concurring with these results in 1969, as NIH threatened to cut off funding for the project, leading both parties to return to work on synthesis. Schally and Guillemin shared the 1977

Nobel Prize in Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...

''"for their discoveries concerning the peptide hormone production of the brain."'' News accounts of their work often focused on their "fierce competition" and use of a very large amount of sheep and pig brains to locate the hormone.

Clinical significance

TRH is used clinically by intravenous injection (brand name Relefact TRH) to test the response of the

anterior pituitary gland A major organ of the endocrine system, the anterior pituitary (also called the adenohypophysis or pars anterior) is the glandular, anterior lobe that together with the posterior lobe (posterior pituitary, or the neurohypophysis) makes up the pi ...

; this procedure is known as a TRH test. This is done as diagnostic test of

thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thyr ...

disorders such as secondary

hypothyroidism Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as po ...

and in

acromegaly Acromegaly is a disorder that results from excess growth hormone (GH) after the growth plates have closed. The initial symptom is typically enlargement of the hands and feet. There may also be an enlargement of the forehead, jaw, and nose. Othe ...

. TRH has anti-depressant and anti-suicidal properties, and in 2012 the U.S. Army awarded a research grant to develop a TRH nasal spray in order to prevent suicide amongst its ranks. The antidepressant properties of TRH are present when TRH is administered intrathecally, or administration into the spine, and the effects are short-lived. Some researchers are testing a prodrug approach to administer TRH orally and have TRH reach the brain without being degraded in the stomach or blood. TRH has been shown in mice to be an anti-aging agent with a broad spectrum of activities that, because of their actions, suggest that TRH has a fundamental role in the regulation of metabolic and hormonal functions.

Side effects

Side effects after intravenous TRH administration are minimal. Nausea, flushing, urinary urgency, and mild rise in blood pressure have been reported. After

intrathecal Intrathecal administration is a route of administration for drugs via an injection into the spinal canal, or into the subarachnoid space so that it reaches the cerebrospinal fluid (CSF) and is useful in spinal anesthesia, chemotherapy, or pain ma ...

administration, shaking, sweating, shivering, restlessness, and mild rise in blood pressure were observed.

References

External links

* {{DEFAULTSORT:Thyrotropin-Releasing Hormone Galactagogues Hormones of the hypothalamus Hormones of the hypothalamus-pituitary-adrenal axis Hormones of the hypothalamic-pituitary-prolactin axis Peptide hormones Thyroid Tripeptides