Thymosin

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NMR structure of the bovine b9-thymosin polypeptide based on the PDB 1HJ0 coordinates. Thymosin 1HJ0.png
NMR structure of the bovine β9-thymosin polypeptide based on the PDB 1HJ0 coordinates.

Thymosins are small proteins present in many animal tissues. They are named thymosins because they were originally isolated from the thymus, but most are now known to be present in many other tissues. [1] Thymosins have diverse biological activities, and two in particular, thymosins α1 and β4, have potentially important uses in medicine, some of which have already progressed from the laboratory to the clinic. In relation to diseases, thymosins have been categorized as biological response modifiers. [2]

Thymus Organ Of The Immune System

The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, T cells mature. T cells are critical to the adaptive immune system, where the body adapts specifically to foreign invaders. The thymus is composed of two identical lobes and is located anatomically in the anterior superior mediastinum, in front of the heart and behind the sternum. Histologically, each lobe of the thymus can be divided into a central medulla and a peripheral cortex which is surrounded by an outer capsule. The cortex and medulla play different roles in the development of T cells. Cells in the thymus can be divided into thymic stromal cells and cells of hematopoietic origin. Developing T cells are referred to as thymocytes and are of hematopoietic origin. Stromal cells include epithelial cells of the thymic cortex and medulla, and dendritic cells.

Contents

Discovery

The discovery of thymosins in the mid 1960s emerged from investigations of the role of the thymus in development of the vertebrate immune system. Begun by Allan L. Goldstein in the Laboratory of Abraham White at the Albert Einstein College of Medicine in New York, the work continued at University of Texas Medical Branch in Galveston and at The George Washington University School of Medicine and Health Sciences in Washington D.C. The supposition that the role of the thymus might involve a hormone-like mechanism led to the isolation from thymus tissue of a biologically active preparation. Known as "Thymosin Fraction 5", this was able to restore some aspects of immune function in animals lacking thymus gland. Fraction 5 was found to contain over 40 small peptides (molecular weights ranging from 1000 to 15,000 Da.), [3] which were named "thymosins" and classified as α, β and γ thymosins on the basis of their behaviour in an electric field. Although found together in Fraction 5, they are now known to be structurally and genetically unrelated. Thymosin β1 was found to be ubiquitin (truncated by two C-terminal glycine residues). [4]

Immune system A biological system that protects an organism against disease

The immune system is a host defense system comprising many biological structures and processes within an organism that protects against disease. To function properly, an immune system must detect a wide variety of agents, known as pathogens, from viruses to parasitic worms, and distinguish them from the organism's own healthy tissue. In many species, there are two major subsystems of the immune system: the innate immune system and the adaptive immune system. Both subsystems use humoral immunity and cell-mediated immunity to perform their functions. In humans, the blood–brain barrier, blood–cerebrospinal fluid barrier, and similar fluid–brain barriers separate the peripheral immune system from the neuroimmune system, which protects the brain.

Allan L. Goldstein

Allan L. Goldstein is Emeritus Professor in the Department of Biochemistry and Molecular Medicine at the George Washington University School of Medicine. He chaired the department from 1978 until March 2009 and was awarded Emeritus status in 2013. He is an authority on the thymus gland and the workings of the immune system, and co-discoverer of the Thymosins, a family of hormone-like peptides isolated from the thymus gland.

Hormone chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism

A hormone is any member of a class of signaling molecules, produced by glands in multicellular organisms, that are transported by the circulatory system to target distant organs to regulate physiology and behavior. Hormones have diverse chemical structures, mainly of three classes:

When individual thymosins were isolated from Fraction 5 and characterized, they were found to have extremely varied and important biological properties. However they are not truly thymic hormones in that they are not restricted in occurrence to thymus and several are widely distributed throughout many different tissues. [3] [4] [5]

Doping in sports

Thymosin beta-4 was allegedly used by some players in various Australian football codes and is under investigation by the Australian Sports Anti-Doping Authority for anti-doping violations. [6] [7]

Thymosin beta-4 mammalian protein found in Homo sapiens

Thymosin beta-4 is a protein that in humans is encoded by the TMSB4X gene. Recommended INN for thymosin beta-4 is 'timbetasin', as published by the World Health Organization (WHO).

Thymosin as a hair loss treatment

The process of hair growth utilizes many cellular and molecular mechanisms common to angiogenesis and wound healing. While studying the influence of thymosin beta-4 (Tβ4) on wound healing, Philp et al. accidentally found that hair grew more rapidly around the edges of wounds. In due course, they showed that Tβ4 induced rapid hair growth on the dorsal skin of healthy mice. [8]

See also

Related Research Articles

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Proopiomelanocortin mammalian protein found in Homo sapiens

Pro-opiomelanocortin (POMC) is a precursor polypeptide with 241 amino acid residues. POMC is synthesized in the pituitary from the 285-amino-acid-long polypeptide precursor pre-pro-opiomelanocortin (pre-POMC), by the removal of a 44-amino-acid-long signal peptide sequence during translation.

Progestogen

Progestogens, also sometimes written progestagens or gestagens, are a class of steroid hormones that bind to and activate the progesterone receptor (PR). Progesterone is the major and most important progestogen in the body. The progestogens are named for their function in maintaining pregnancy, although they are also present at other phases of the estrous and menstrual cycles.

Androstenedione chemical compound

Androstenedione, or 4-androstenedione, also known as androst-4-ene-3,17-dione, is an endogenous weak androgen steroid hormone and intermediate in the biosynthesis of estrone and of testosterone from dehydroepiandrosterone (DHEA). It is closely related to androstenediol (androst-5-ene-3β,17β-diol).

Dihydrotestosterone chemical compound

Dihydrotestosterone is an endogenous androgen sex steroid and hormone. The enzyme 5α-reductase catalyzes the formation of DHT from testosterone in certain tissues including the prostate gland, seminal vesicles, epididymides, skin, hair follicles, liver, and brain. This enzyme mediates reduction of the C4-5 double bond of testosterone. Relative to testosterone, DHT is considerably more potent as an agonist of the androgen receptor (AR).

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HSD17B2 protein-coding gene in the species Homo sapiens

17β-Hydroxysteroid dehydrogenase 2 (17β-HSD2) is an enzyme of the 17β-hydroxysteroid dehydrogenase (17β-HSD) family that in humans is encoded by the HSD17B2 gene.

IDH3B protein-coding gene in the species Homo sapiens

Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial is an enzyme that in humans is encoded by the IDH3B gene.

Thymulin chemical compound

Thymulin is a nonapeptide produced by two distinct epithelial populations in the thymus first described by Bach in 1977. It requires zinc for biological activity. Its peptide sequence is H-Pyr-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn-OH.

TMSB15A protein-coding gene in the species Homo sapiens

Thymosin beta-15A is a protein that in humans is encoded by the TMSB15A gene.

Thymosin beta-15B is a protein that, in humans, is encoded by the TMSB15B gene. The protein is identical in aminoacid sequence to Thymosin beta-15A, product of the TMSB15A gene, although synthesis of the two proteins is independently regulated.

Thymosin α1 protein-coding gene in the species Homo sapiens

Thymosin α1 is a peptide fragment derived from prothymosin alpha, a protein that in humans is encoded by the PTMA gene.

Beta thymosins

Beta thymosins are a family of proteins which have in common a sequence of about 40 amino acids similar to the small protein thymosin β4. They are found almost exclusively in multicellular animals. Thymosin β4 was originally obtained from the thymus in company with several other small proteins which although named collectively "thymosins" are now known to be structurally and genetically unrelated and present in many different animal tissues.

Alfatradiol medication

Alfatradiol, also known as 17α-estradiol and sold under the brand names Avicis, Avixis, Ell-Cranell Alpha, and Pantostin, is a weak estrogen and 5α-reductase inhibitor medication which is used topically in the treatment of pattern hair loss in men and women. It is a stereoisomer of the endogenous steroid hormone and estrogen 17β-estradiol.

3β-Androstanediol chemical compound

3β-Androstanediol, also known as 5α-androstane-3β,17β-diol, and often shortened to 3β-diol, is an endogenous steroid hormone. It is a 5α-reduced and 17β-hydroxylated metabolite of dehydroepiandrosterone (DHEA) as well as a 3β-hydroxylated metabolite of dihydrotestosterone (DHT). 3β-Diol is a selective, potent, high-affinity full agonist of the ERβ, and hence, an estrogen. It has higher affinity for this receptor than estradiol. In contrast to ERβ, 3β-diol does not bind to the androgen receptor (AR). 3β-Diol has been reported to also bind to ERα with low nanomolar affinity, with several-fold lower affinity relative to ERβ. It has approximately 3% and 7% of the affinity of estradiol at the ERα and ERβ, respectively. Unlike its 3α-isomer, 3α-androstanediol (3α-diol), 3β-diol does not bind to the GABAA receptor.

Etiocholanedione chemical compound

Etiocholanedione, also known as 5β-androstanedione or as etiocholane-3,17-dione, is a naturally occurring etiocholane (5β-androstane) steroid and an endogenous metabolite of androgens like testosterone, dihydrotestosterone, dehydroepiandrosterone (DHEA), and androstenedione. It is the C5 epimer of androstanedione (5α-androstanedione). Although devoid of androgenic activity like other 5β-reduced steroids, etiocholanedione has some biological activity of its own. The compound has been found to possess potent haematopoietic effects in a variety of models. In addition, it has been found to promote weight loss in animals and in a double-blind, placebo-controlled clinical study in humans conducted in 1993. These effects are said to be similar to those of DHEA. Unlike DHEA however, etiocholanedione cannot be metabolized further into steroid hormones like androgens and estrogens.

References

Notes
  1. Hannappel, E; Huff, T (2003). "The thymosins. Prothymosin alpha, parathymosin, and beta-thymosins: structure and function". Vitamins and hormones. 66: 257–96. PMID   12852257.
  2. Low, TL; Goldstein, AL (1984). "Thymosins: structure, function and therapeutic applications". Thymus. 6 (1–2): 27–42. PMID   6087503.
  3. 1 2 Goldstein AL (September 2007). "History of the discovery of the thymosins". Ann. N. Y. Acad. Sci. 1112: 1–13. doi:10.1196/annals.1415.045. PMID   17600284.
  4. 1 2 Hannappel E (September 2007). "beta-Thymosins". Ann. N. Y. Acad. Sci. 1112: 21–37. doi:10.1196/annals.1415.018. PMID   17468232.
  5. Garaci E (September 2007). "Thymosin alpha1: a historical overview". Ann. N. Y. Acad. Sci. 1112: 14–20. doi:10.1196/annals.1415.039. PMID   17567941.
  6. Ho, EN; Kwok, WH; Lau, MY; Wong, AS; Wan, TS; Lam, KK; Schiff, PJ; Stewart, BD (23 November 2012). "Doping control analysis of TB-500, a synthetic version of an active region of thymosin β₄, in equine urine and plasma by liquid chromatography-mass spectrometry". Journal of Chromatography A. 1265: 57–69. doi:10.1016/j.chroma.2012.09.043. PMID   23084823.
  7. https://theconversation.edu.au/cronulla-sharks-and-thymosin-beta-4-is-it-doping-12694 (Feb/Mar 2013)
  8. "Triggering Hair Growth at a Cellular Level". 2017-04-16. Retrieved 2017-04-21.
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