Activin na inhibin

inhibin, alpha
Ihe ndị na-eme ka a mata ya
Ihe nnọchianya INHA
Mkpụrụ ndụ ihe nketa NCBI 3623
HGNC 6065
OMIM 147380
RefSeq NM_002191
UniProt P05111
Ihe ọmụma ndị ọzọ
Locus Ihe e dere n'ala 2 q33-qter
Ịchọta
Ihe owuwu Ihe nlereanya Switzerland
Ógbè InterPro
inhibin, beta E
Ihe ndị na-eme ka a mata ya
Ihe nnọchianya INHBE
Alt. akara activin E
Mkpụrụ ndụ ihe nketa NCBI 83729
HGNC 24029
OMIM 612031
RefSeq NM_031479
UniProt P58166
Ihe ọmụma ndị ọzọ
Locus Ihe e dere n'ala 12 q13.2
Ịchọta
Ihe owuwu Ihe nlereanya Switzerland
Ógbè InterPro

Activin na inhibin bụ ogige protein abụọ nwere njikọ chiri anya nke nwere ihe fọrọ nke nta ka ọ bụrụ ihe na-emegide mmetụta ndu. Achọpụtara na 1986, [1] [2] activin na-akwalite biosynthesis FSH na nzuzo, ma na-ekere òkè na nhazi usoro nsọ nwanyị. Achọpụtala ọtụtụ ọrụ ndị ọzọ na-arụ ọrụ site na activin, gụnyere ọrụ na mgbasawanye cell, ọdịiche dị iche iche, apoptosis, [3] metabolism, homeostasis, nzaghachi mgbochi, nrụzi ọnya, [4] na ọrụ endocrine. N'aka nke ọzọ, inhibin na-ebelata njikọ FSH ma na-egbochi nzuzo FSH.[5] Achọpụtara ịdị adị nke inhibin dị ka n'oge 1916; Otú ọ dị, egosighi na ọ dị adị ruo mgbe ọrụ Neena Schwartz na Cornelia Channing n'etiti 1970s, mgbe nke ahụ gasịrị, e ji mara protein abụọ ahụ n'ụdị molecular afọ iri ka e mesịrị.[1]

Activin bụ dimer nke nwere akụkụ abụọ yiri ibe ha ma ọ bụ yiri ibe ha. Inhibin bụkwa dimer ebe akụkụ mbụ bụ beta subunit yiri ma ọ bụ yiri beta subunit na activin. Otú ọ dị, n'adịghị ka activin, akụkụ nke abụọ nke inhibin dimer bụ subunit alpha nwere njikọ dị anya.[2][3] Activin, inhibin na ọtụtụ protein ndị ọzọ nwere njikọ dị ka hormone anti-Müllerian, protein morphogenetic nke ọkpụkpụ, na ihe dị iche iche nke uto bụ nke superfamily protein TGF-β.[4]

Ọdịdị ya

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Ngwakọta protein activin na inhibin bụ akụkụ nke dimeric na nhazi ya, na, na mgbagwoju nke ọ bụla, monomers abụọ na-ejikọta ibe ha site na otu disulfide bond.[1]. Na mgbakwunye, ogige abụọ ahụ sitere n'otu ezinụlọ nke mkpụrụ ndụ ihe nketa na protein metụtara mana ha dị iche na nhazi nke subunit ha.[2]. N'okpuru ebe a bụ ndepụta nke ogige inhibin na activin a na-ahụkarị na ihe mejupụtara ha:   Alpha na beta subunits nwere ihe dịka 25% nke usoro yiri, ebe ihe yiri n'etiti beta subunites bụ ihe dịka 65%.[4]

N'imE <su sub="">B id="mwSw">A ndị na-enye nwa ara, akọwaala subunits beta anọ, a na-akpọ aC βA, activin βB, activin betaC na activin βE. </su><su sub="">B id="mwTw">A βA na βB yiri nke abụọ beta subunits nke inhibin. </su>A kọwawo akụkụ nke ise, activin βD, na Xenopus laevis. <su sub="">B id="mwVA">A A nke activin βA na-ebute activin A, otu βA, na otu βB na-ebulite activin AB, na ihe ndị ọzọ. </su>A kọwaala heterodimers dị iche iche, mana ọ bụghị ha niile ga-ekwe omume.[5][6] A na-ejikọta subunits site na otu njikọ covalent disulfide.

SuB <A class="cx-link" data-linkid="522" href="./INHBC" id="mwXA" rel="mw:WikiLink" title="INHBC">βC nwere ike ịmepụta activin heterodimers na βA ma ọ bụ βB subunits mana enweghị ike iji inhibin α dimerize.[7]

Ọrụ

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Ihe na-akpali akpali

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A na-emepụta activin na gonads, pituitary gland, Placenta, na akụkụ ndị ọzọ:

  • Na follicle ovarian, activin na-eme ka njikọ FSH na FSH-induced aromatization dịkwuo elu. Ọ na-ekere òkè na njikọ androgen na-eme ka ọrụ LH dịkwuo mma na Ovary na testi. N'ime nwoke, activin na-eme ka spermatogenesis dịkwuo elu.
  • A na-egosipụta activin n'ụzọ siri ike na akpụkpọ ahụ merụrụ ahụ, na ngosipụta gabigara ókè nke activin na epidermis nke òké transgenic na-eme ka ọgwụgwọ ọnyá dịkwuo mma ma na-emeziwanye mmepụta ọnyá. Ọrụ ya na mmezi ọnyá na morphogenesis akpụkpọ ahụ bụ site na ịkpali keratinocytes na mkpụrụ ndụ stromal n'ụzọ dabere na ọgwụ.[8]
  • Activin na-achịkwa morphogenesis nke akụkụ ahụ dị iche iche dị ka prostate, akpa ume, na karịsịa akụrụ. Activin A mụbara ọkwa ngosipụta nke ụdị-I collagen na-atụ aro na activin A na-arụ ọrụ dị ka onye na-akpali Fibroblasts.
  • Enweghị activin n'oge mmepe na-ebute nkwarụ mmepe akwara.
  • Upregulation nke Activin A na-akpali mkpụrụ ndụ stem pluripotent n'ime akara mesoendodermal, ma si otú a na-enye ngwá ọrụ bara uru maka ọdịiche nke mkpụrụ ndụ stem na mmepụta organoid.[9]

Inhibin

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Na ụmụ nwanyị na ụmụ nwoke, inhibin na-egbochi mmepụta FSH. Inhibin anaghị egbochi mmepụta nke GnRH site na hypothalamus. [10][11] Otú ọ dị, usoro ahụ dum dị iche n'etiti ụmụ nwoke na ụmụ nwanyị:

N'ime ụmụ nwanyị

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A na-emepụta inhibin na gonads, pituitary gland, Placenta, corpus luteum na akụkụ ndị ọzọ.

FSH na-akpali mmepụta nke inhibin site na mkpụrụ ndụ granulosa nke follicles ovarian na ovaries. N'aka nke ya, inhibin na-egbochi FSH.

  • Inhibin B na-eru n'elu n'oge mmalite ruo n'etiti follicular, na n'elu nke abụọ na ovulation.
  • Inhibin A na-eru n'ókè ya n'etiti oge ọgụ.

N'ime ụmụ nwoke

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It is secreted from the Sertoli cells,[12] located in the seminiferous tubules inside the testes. Androgens stimulate inhibin production; this protein may also help to locally regulate spermatogenesis.[13]

Usoro nke ọrụ

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Ihe na-akpali akpali

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Dị ka ndị ọzọ so n'ezinụlọ ahụ, activins na-emekọrịta ihe na ụdị abụọ nke ndị na-anabata transmembrane n'elu mkpụrụ ndụ (Ụdị I na II) nke nwere ọrụ serine / threonine kinase intrinsic na ngalaba cytoplasmic ha:

  • Activin ụdị 1 receptors: ACVR1, ACVR1B, ACVR1C
  • Ndị na-anabata ụdị 2 nke Activin: ACVR2A, ACVR2B

Activin na-ejikọta na onye na-anabata Ụdị II ma malite mmeghachi omume cascade nke na-eduga na recruitment, phosphorylation, na ịrụ ọrụ nke onye na-anata ụdị I activin. Nke a na-emekọrịta ihe na phosphorylates SMAD na SMAD3, abụọ n'ime protein SMAD cytoplasmic.

Smad3 na-agagharị na nucleus ma na-emekọrịta ihe na SMAD4 site na multimerization, na-akpata mgbanwe ha dị ka ihe mgbagwoju anya nke transcription na-ahụ maka ngosipụta nke ọtụtụ mkpụrụ ndụ ihe nketa.

Inhibin

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N'adịghị ka activin, a maghị ihe dị ukwuu banyere usoro ọrụ nke inhibin, mana ọ nwere ike ịgụnye ịsọ mpi na activin maka ijikọta na ndị na-anabata activin na / ma ọ bụ ijikọta ya na ndị na'anabata inhibin.[3]

Ihe ọ pụtara n'ihe gbasara ahụike

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Ihe na-akpali akpali

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Activin A dị ọtụtụ n'ime abụba abụba nke ndị buru oke ibu, ma e jiri ya tụnyere ndị na-adịghị ike.[14] Activin A na-akwalite mmụba nke mkpụrụ ndụ nna adipocyte, ka ọ na-egbochi ọdịiche ha n'ime adipocytes.[14] Activin A na-amụba cytokines inflammatory na macrophages.[14]

mgbanwe na mkpụrụ ndụ ihe nketa maka onye na-anabata activin ACVR1 na-ebute fibrodysplasia ossificans progressiva, ọrịa na-egbu egbu nke na-eme ka uru ahụ na anụ ahụ dị nro jiri nwayọọ nwayọọ dochie anya anụ ahụ ọkpụkpụ.[15] A na-akọwa ọnọdụ a site n'ịmepụta ọkpụkpụ ọzọ nke na-emepụta immobilization na n'ikpeazụ ọnwụ site na iku ume.[15] Mgbanwe na ACVR1 na-akpata activin A, nke na-arụkarị ọrụ dị ka onye na-emegide onye na-anabata ma na-egbochi osteogenesis (ọkpụkpụ uto), iji mee ka onye na'ahụ maka onye na-anata ya ma mee ka ọkpụkpụ na-eto eto.[15] Na 2 Septemba 2015, Regeneron Pharmaceuticals kwupụtara na ha mepụtara ihe na-alụso ọrịa ọgụ maka activin A nke na-agwọ ọrịa ahụ n'ụzọ dị irè na ihe nlereanya anụmanụ nke ọnọdụ ahụ.[16]

A na-ejikọkwa mgbanwe na mkpụrụ ndụ ihe nketa ACVR1 na ọrịa kansa, ọkachasị diffuse intrinsic pontine glioma (DIPG).[17][18][19]

Ọnọdụ dị elu nke Activin B na ọkwa Activin A dị mma nyere ihe na-egosi ihe ga-eme ka ọ bụrụ ihe na-eme ka ọrịa myalgic encephalomyelitis / ọrịa ike ọgwụgwụ na-adịghị ala.[20]

Activin A na-egosipụta oke n'ọtụtụ ọrịa kansa. E gosipụtara na ọ na-akwalite tumorigenesis site na igbochi mmeghachi omume mgbochi tumor na melanoma.[21]

Inhibin

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Nkọwa nke inhibin A bụ akụkụ nke ihe nyocha quad tupu a mụọ nwa nke enwere ike inye n'oge ime n'oge afọ ime nke izu 16-18. Inhibin A dị elu (yana beta-hCG dị elu, AFP belatara, na estriol belatara) na-egosi ọnụnọ nke nwa e bu n'afọ nwere Ọrịa Down.[22] Dị ka ule nyocha, a ghaghị ịgbaso nsonaazụ nyocha quad na-adịghị mma na nyocha ndị ọzọ doro anya.

A na-ejikwa ya eme ihe dị ka ihe na-egosi Ọrịa kansa ovarian.[23][24]

Enwere ike iji Inhibin B mee ihe dị ka akara nke ọrụ spermatogenesis na enweghị ọmụmụ nwoke. Ọkwa ọbara inhibin B dị elu nke ukwuu n'etiti ụmụ nwoke nwere ike ime (ihe dị ka 140 pg/mL) karịa na ụmụ nwoke na-amụghị nwa (ihe dị ka 80 pg/ml).[1] N'ime ndị ikom nwere azoospermia, nyocha dị mma maka inhibin B na-ebuli ohere iji nweta afọ ime nke ọma site na mmịpụta sperm testicular (TESE), ọ bụ ezie na njikọ ahụ adịchaghị mkpa, na-enwe mmetụta nke 0.65 (95% oge ntụkwasị obi [CI]: 0.56 -0.74) na nkọwapụta nke 0.83 (CI: 0.64-0.93) maka amụma ọnụnọ nke spam na testes na azoospermia na-abụghị obstructive..[25]

Ebem si dee

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  1. ↑ (October 2014) "Inhibin at 90: from discovery to clinical application, a historical review". Endocrine Reviews 35 (5): 747–94. DOI:10.1210/er.2014-1003. PMID 25051334. 
  2. ↑ (April 1988) "Inhibin: definition and nomenclature, including related substances". The Journal of Clinical Endocrinology and Metabolism 66 (4): 885–6. PMID 3346366. 
  3. ↑ 3.0 3.1 (March 2004) "Inhibin/activin and ovarian cancer". Endocrine-Related Cancer 11 (1): 35–49. DOI:10.1677/erc.0.0110035. PMID 15027884.  Kpọpụta njehie: Invalid <ref> tag; name "pmid15027884" defined multiple times with different content
  4. ↑ 4.0 4.1 (Jan 1994) "The TGF-beta superfamily: new members, new receptors, and new genetic tests of function in different organisms". Genes & Development 8 (2): 133–46. DOI:10.1101/gad.8.2.133. PMID 8299934.  Kpọpụta njehie: Invalid <ref> tag; name "pmid8299934" defined multiple times with different content
  5. ↑ (November 2006) "The role of activin in neuropeptide induction and pain sensation". Developmental Biology 299 (2): 303–9. DOI:10.1016/j.ydbio.2006.08.026. PMID 16973148. 
  6. ↑ (March 2008) "Activins and activin antagonists in hepatocellular carcinoma". World Journal of Gastroenterology 14 (11): 1699–709. DOI:10.3748/wjg.14.1699. PMID 18350601. 
  7. ↑ (December 2000) "Localization of activin beta(A)-, beta(B)-, and beta(C)-subunits in humanprostate and evidence for formation of new activin heterodimers of beta(C)-subunit". The Journal of Clinical Endocrinology and Metabolism 85 (12): 4851–8. DOI:10.1210/jcem.85.12.7052. PMID 11134153. 
  8. ↑ Bamberger (2021-03-09). "Activin Controls Skin Morphogenesis and Wound Repair Predominantly via Stromal Cells and in a Concentration-Dependent Manner via Keratinocytes". The American Journal of Pathology 167 (3): 733–747. DOI:10.1016/S0002-9440(10)62047-0. PMID 16127153. 
  9. ↑ (2015) "Activin/Nodal signalling in stem cells". Development 142 (4): 607–19. DOI:10.1242/dev.091769. PMID 25670788. 
  10. ↑ (2005) "Inhibins in female and male reproductive physiology: role in gametogenesis, conception, implantation and early pregnancy". Human Reproduction Update 11 (2): 123–35. DOI:10.1093/humupd/dmh057. PMID 15618291. 
  11. ↑ (2012) First Aid for the USMLE Step 1. McGraw Hill. ISBN 978-0-07-177636-3. 
  12. ↑ (October 1989) "Stimulation of Sertoli cell inhibin secretion by the testicular paracrine factor PModS". Molecular and Cellular Endocrinology 66 (2): 239–49. DOI:10.1016/0303-7207(89)90036-1. PMID 2515083. 
  13. ↑ (November 2001) "Inhibin B in male reproduction: pathophysiology and clinical relevance". European Journal of Endocrinology 145 (5): 561–71. DOI:10.1530/eje.0.1450561. PMID 11720872. 
  14. ↑ 14.0 14.1 14.2 (2010) "Activin a plays a critical role in proliferation and differentiation of human adipose progenitors". Diabetes 59 (10): 2513–2521. DOI:10.2337/db10-0013. PMID 20530742. 
  15. ↑ 15.0 15.1 15.2 (May 2006) "A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva". Nature Genetics 38 (5): 525–527. DOI:10.1038/ng1783. PMID 16642017. 
  16. ↑ Julie Steenhuysen (2 September 2015). Regeneron scientists discover key to excess bone growth in rare disease. Reuters.
  17. ↑ (May 2014) "Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma". Nature Genetics 46 (5): 457–61. DOI:10.1038/ng.2925. PMID 24705252. 
  18. ↑ Cure Brain Cancer - News - Multiple Breakthroughs in Childhood Brain Cancer DIPG. Cure Brain Cancer Foundation.
  19. ↑ (May 2014) "Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations". Nature Genetics 46 (5): 451–6. DOI:10.1038/ng.2936. PMID 24705254. 
  20. ↑ (March 2017) "Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study". Journal of Translational Medicine 15 (1): 60. DOI:10.1186/s12967-017-1161-4. PMID 28302133. 
  21. ↑ (December 2017) "Paracrine Activin-A Signaling Promotes Melanoma Growth and Metastasis through Immune Evasion". The Journal of Investigative Dermatology 137 (12): 2578–2587. DOI:10.1016/j.jid.2017.07.845. PMID 28844941. 
  22. ↑ (May 1996) "Dimeric inhibin A as a marker for Down's syndrome in early pregnancy". The New England Journal of Medicine 334 (19): 1231–6. DOI:10.1056/NEJM199605093341904. PMID 8606718. 
  23. ↑ (April 2007) "Inhibin as a diagnostic marker for ovarian cancer". Cancer Letters 249 (1): 14–7. DOI:10.1016/j.canlet.2006.12.017. PMID 17320281. 
  24. ↑ (October 2004) "Inhibins and ovarian cancer". Molecular and Cellular Endocrinology 225 (1–2): 65–71. DOI:10.1016/j.mce.2004.02.014. PMID 15451569. 
  25. ↑ (2010) "Inhibin B and anti-Mullerian hormone as markers of persistent spermatogenesis in men with non-obstructive azoospermia: a meta-analysis of diagnostic accuracy studies". Human Reproduction Update 16 (6): 713–24. DOI:10.1093/humupd/dmq024. PMID 20601364.