24305-27-9 Usage
Description
Protirelin, also known as Thyrotropin-Releasing Hormone (TRH), is a hypothalamic hypophysiotropic neuropeptide that serves as the first hypothalamic hypophysiotropic neurohormone identified. It consists of the tripeptide pGlu-His-ProNH2 and is responsible for stimulating the secretion of thyroid-stimulating hormone (TSH), prolactin (PRL), and growth hormone (GH). In addition to its endocrine functions, TRH also acts as a neurotransmitter and neuromodulator. It is a white or yellowish-white powder that is hygroscopic in nature.
Uses
Used in Endocrinology:
Protirelin is used as a diagnostic agent for the assessment of thyroid function. It helps in the evaluation of patients with suspected hypothalamic or pituitary dysfunction by stimulating the release of TSH, PRL, and GH.
Used in Neurology:
As a neurotransmitter and neuromodulator, Protirelin is used in the study and treatment of various neurological disorders. It has been found to have potential therapeutic applications in conditions such as depression, Alzheimer's disease, and spinal cord injuries.
Used in Wound Healing:
Protirelin is used as a therapeutic agent to accelerate wound healing. Its ability to stimulate the release of growth hormone and other factors contributes to the promotion of tissue repair and regeneration.
Used in Anticancer Applications:
Although not explicitly mentioned in the provided materials, Protirelin has been studied for its potential role in cancer treatment. It has been shown to modulate several oncological signaling pathways, which could potentially be harnessed for therapeutic purposes in cancer patients.
Used in Drug Delivery Systems:
Similar to Gallotannin, Protirelin could potentially be incorporated into novel drug delivery systems to enhance its applications and efficacy. These systems could improve the delivery, bioavailability, and therapeutic outcomes of Protirelin in various medical applications.
Discovery
TRH was first isolated and characterized in 1969 by
Roger Guillemin and Andrew Schally, who shared the
Nobel Prize in Physiology or Medicine in 1977 “for their
discoveries concerning the peptide hormone production
of the brain.”The biosynthesis of TRH from a precursor molecule was first clarified in 1984 by isolation of a
preproTRH cDNA from the skin of Xenopus laevis.? The
structure of the TRH receptor (TRH-R) was first deduced
from a cDNA isolated from the mouse pituitary in 1990.
Properties
Mr 362. Soluble in water, methanol, and ethanol; partially insoluble in chloroform; completely insoluble in
ether and pyridine. Stable in solution at <15°C for more
than a year; partially (1%) degraded at 40°C for 6 months.
Resistant to proteolytic enzymes. Inactivated by diazotized sulfanilic acid (Pauly reagent). Plasma half-life is
2–6min.
Synthesis and release
TRH secretion is regulated by norepinephrine, histamine, dopamine, and serotonin. Cold-induced secretion
of TSH from the rat anterior pituitary involves
α-adrenergic regulation of TRH secretion. TRH neurons
in the PVN are negatively regulated by thyroid hormones
through a feedback mechanism. Locally produced T3 is
taken by these neurons to regulate transcription, posttranslational modification, and degradation of TRH.
Gene, mRNA, and precursor
TRH is synthesized from a precursor that contains
multiple copies of the TRH progenitor sequence GlnHis-Pro-Gly, which is flanked by dibasic cleavage sites
at its N- and C-termini. The number of progenitor sequences in a precursor is diversified: six in humans,
five in rats, four in chicken, seven in frogs, and six to eight
in fish. Human preproTRH gene, TRH, location 3q13.3–q21, consists of three exons.
Clinical implications
The majority of thyroid disfunction is due to primary
thyroid disease. On the other hand, central thyroid disfunction is related to a disorder of the pituitary (TSH),
hypothalamus (TRH), or hypothalamic-pituitary portal
circulation. Isolated central hypothyroidism was
reported in a patient with inactivating mutations in the
TRH-R gene.
Receptors
TRH-R is a seven-transmembrane-domain GPCR. Two
major types of TRH-Rs (type I receptor including TRH-R1
and TRH-R3, and type II receptor [TRH-R2]), have been
identified in vertebrates . Three and four subtypes of TRH-Rs have been identified in Xenopus laevis
and teleost species, respectively.?TRH action is mediated via a membrane receptor
mainly coupled to Gq/11 protein. TRH induces the mobilization of intracellular Ca2+ and the activation of PKC in
target cells.
Biological functions
The Trh knockout mice show normal development,
but exhibit tertiary hypothyroidism and hyperglycemia
due to diminished insulin secretion. The Trh knockout
mice show defects in cerebellar long-term depression
and a motor learning deficit.The Trhr1 knockout mice
exhibit central hypothyroidism showing a decrease in
serum T3, T4, and PRL levels but not in serum TSH?levels. The Trhr1 knockout mice exhibit normal growth
and development but displayed increased anxiety and
depression levels. The Trhr2 knockout mice are euthyroid with normal serum TSH levels and exhibit normal
development and growth. The mutant females exhibited
moderately increased depression and reduced anxiety
phenotypes.
Indications
Thyrotropin-releasing hormone, or protirelin, consists
of three amino acids. TRH (Relefact TRH) is used for
tests to distinguish primary from secondary hypothyroidism.
Biochem/physiol Actions
Thyrotropin releasing hormone (TRH) stimulates production and secretion of thyrotropin (TSH) and prolactin from the anterior pituitary. It also plays a vital role as a neurotransmitter and neuromodulator.
Clinical Use
TRH (200–500μg) administered intravenously to normal subjects causes a rise in TSH levels within
15–30min, resulting in an increase in T3 levels within
90–150min. In primary hypothyroidism, TSH hyperresponse to TRH occurs, with a typical elevation in the
basal TSH levels. In secondary (pituitary) hypothyroidism, an impaired TSH response to TRH occurs, whereas
in tertiary (hypothalamic) hypothyroidism normal or
increased TSH response to TRH occurs. Protirelin is used
to test the response of the anterior pituitary to TRH in
people who may have medical conditions of thyroid
function, including hyperthyroidism, Graves’ disease,
and hypothyroidism. In addition, TRH has been used
to assess the ability of the prolactin secretion in the
pituitary.
Check Digit Verification of cas no
The CAS Registry Mumber 24305-27-9 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 2,4,3,0 and 5 respectively; the second part has 2 digits, 2 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 24305-27:
(7*2)+(6*4)+(5*3)+(4*0)+(3*5)+(2*2)+(1*7)=79
79 % 10 = 9
So 24305-27-9 is a valid CAS Registry Number.
InChI:InChI=1/C16H22N6O4/c17-14(24)12-2-1-5-22(12)16(26)11(6-9-7-18-8-19-9)21-15(25)10-3-4-13(23)20-10/h7-8,10-12H,1-6H2,(H2,17,24)(H,18,19)(H,20,23)(H,21,25)
24305-27-9Relevant articles and documents
A novel peptide synthesis using fluorous chemistry.
Mizuno, Mamoru,Goto, Kohtaro,Miura, Tsuyoshi,Hosaka, Daisuke,Inazu, Toshiyuki
, p. 972 - 973 (2003)
Three new fluorous supports for peptide synthesis, i.e., the trialkoxybenzhydryl-type (6), the Wang-type (7) and the tert-butyl-type support (8), were prepared. A bioactive peptide TRH was easily synthesized by an Fmoc strategy using the benzhydryl-type fluorous support with fluorous chemistry.
Synthesis of the thyrotropin-releasing hormone.
Boler,Chang,Enzmann,Folkers
, p. 475 - 476 (1971)
-
-
Flouret et al.
, p. 53,56 (1972)
-
Synthesis of pyroglutamylhistidylprolineamide by classical and solid phase methods.
Flouret
, p. 843 - 845 (1970)
-
Pressure/Temperature Combined Treatments of Precursors Yield Hormone-like Peptides with Pyroglutamate at the N Terminus
Fernandez Garcia, Avelina,Butz, Peter,Trierweiler, Bernhard,Zoeller, Heike,Staerke, Joachim,Pfaff, Eberhard,Tauscher, Bernhard
, p. 8093 - 8097 (2003)
Peptides containing the cyclic product of glutamine at the N terminus are usually biologically active. If the cyclization of glutamine was associated with a volume reduction, pressure should displace the equilibrium in the direction of the lower volume. Here, results in model solutions and in whey are discussed, showing that the theorized cyclization of glutamine in Gln-His-ProNH2 or Gln-Leu-ProNH2 is significantly accelerated during the application of heat and even more strongly when elevated temperature and pressure combinations are used. The reaction rate depended on the intensity of the pressure treatment, the pH, and the nature of the amino acids adjacent to glutamine. The products of the reaction were identified as thyrotropin-releasing hormone (TRH) and [Leu(2)]TRH. The reported reactions could affect the naturally balanced concentration of short-chain peptides in foods and therefore induce unpredictable biological effects.
The interaction of copper(II) ions with the thyrotropin-releasing hormone synthesized by Adpoc protection
Maskos,Kalbacher,Stock,Voelter
, p. 459 - 466 (1987)
-
Synthesis of thyrotropin-releasing hormone-related peptides using N(α)-tert-butyloxycarbonly-ω-(N-tert- butyloxycarbonylcarbamoyl)-α-amino Acids(1))
Sakura,Hirose,Nishijima,Hashimoto,Okabe,Mi amori,Sato
, p. 3125 - 3127 (1989)
-
Synthesis of Nπ-2-adamantyloxymethylhistidine, His(Nπ-2-Adom), and its evaluation for peptide synthesis
Okada, Yoshio,Wang, Jidong,Yamamoto, Takeshi,Mu, Yu
, p. 753 - 754 (1996)
Nπ-2-Adamantyloxymethylhistidine, His(Nπ-2-Adom), is prepared and successfully applied to the synthesis of thyrotropin-releasing hormone (TRH) in combination with tert-butyloxycarbonyl (Boc) as the Nα-protecting group. This new protecting group suppressed racemization during peptide synthesis and exhibited high solubility in organic solvents.