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Activin na inhibin

Shí Wikipedia, njikotá édémédé nke onyobulạ
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]

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]

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.

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]

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.