Activin and inhibin

{{Short description|Regulators of feedback on FSH-production}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{distinguish|text=the agent that was referred to as 'inhibine' prior to its identification as hydrogen peroxide}} {{Infobox protein | Name = inhibin, alpha | caption = | image = | width = | HGNCid = 6065 | Symbol = INHA | AltSymbols = | EntrezGene = 3623 | OMIM = 147380 | RefSeq = NM_002191 | UniProt = P05111 | PDB = | ECnumber = |Chromosome=2 |Arm=q |Band=33-qter |LocusSupplementaryData = }} {{Infobox protein |Name=inhibin, beta A |image=Peptide hormones - 2ARV.png |caption=The Activin dimer, from 2ARV.pdb |Symbol=INHBA |AltSymbols=activin A |HGNCid=6066 |Chromosome=7 |Arm=p |Band= |LocusSupplementaryData=15-p13 |ECnumber= |OMIM=147290 |EntrezGene=3624 |RefSeq=NM_002192 |UniProt=P08476 |PDB= }} {{Infobox protein |Name=inhibin, beta B |image= |caption= |Symbol=INHBB |AltSymbols=activin B |HGNCid=6067 |Chromosome=2 |Arm= |Band= |LocusSupplementaryData=cen-q13 |ECnumber= |OMIM=147390 |EntrezGene=3625 |RefSeq=NM_002193 |UniProt=P09529 |PDB= }} {{Infobox protein | Name = inhibin, beta C | caption = | image = | width = | HGNCid = 6068 | Symbol = INHBC | AltSymbols = activin C | EntrezGene = 3626 | OMIM = 601233 | RefSeq = NM_005538 | UniProt = P55103 | PDB = | ECnumber = | Chromosome = 12 | Arm = q | Band = 13 | LocusSupplementaryData = }} {{Infobox protein | Name = inhibin, beta E | caption = | image = | width = | HGNCid = 24029 | Symbol = INHBE | AltSymbols = activin E | EntrezGene = 83729 | OMIM = 612031 | RefSeq = NM_031479 | UniProt = P58166 | PDB = | ECnumber = | Chromosome = 12 | Arm = q | Band = 13.2 | LocusSupplementaryData = }}

'''Activin''' and '''inhibin''' are two closely related protein complexes that have almost directly opposite biological effects. Identified in 1986,<ref name="pmid3012369">{{cite journal | vauthors = Vale W, Rivier J, Vaughan J, McClintock R, Corrigan A, Woo W, Karr D, Spiess J | title = Purification and characterization of an FSH releasing protein from porcine ovarian follicular fluid | journal = Nature | volume = 321 | issue = 6072 | pages = 776–9 | year = 1986 | pmid = 3012369 | doi = 10.1038/321776a0 | bibcode = 1986Natur.321..776V | s2cid = 4365045 }}</ref><ref name="pmid3086749">{{cite journal | vauthors = Ling N, Ying SY, Ueno N, Shimasaki S, Esch F, Hotta M, Guillemin R | title = Pituitary FSH is released by a heterodimer of the beta-subunits from the two forms of inhibin | journal = Nature | volume = 321 | issue = 6072 | pages = 779–82 | year = 1986 | pmid = 3086749 | doi = 10.1038/321779a0 | bibcode = 1986Natur.321..779L | s2cid = 38100413 }}</ref> activin enhances FSH biosynthesis and secretion, and participates in the regulation of the menstrual cycle. Many other functions have been found to be exerted by activin, including roles in cell proliferation, differentiation, apoptosis,<ref name="pmid16636301">{{cite journal | vauthors = Chen YG, Wang Q, Lin SL, Chang CD, Chuang J, Chung J, Ying SY | title = Activin signaling and its role in regulation of cell proliferation, apoptosis, and carcinogenesis | journal = Experimental Biology and Medicine | volume = 231 | issue = 5 | pages = 534–44 | date = May 2006 | pmid = 16636301 | doi = 10.1177/153537020623100507 | s2cid = 39050907 | url = http://www.ebmonline.org/cgi/pmidlookup?view=long&pmid=16636301 | url-access = subscription }}</ref> metabolism, homeostasis, immune response, wound repair,<ref name="pmid15451577">{{cite journal | vauthors = Sulyok S, Wankell M, Alzheimer C, Werner S | title = Activin: an important regulator of wound repair, fibrosis, and neuroprotection | journal = Molecular and Cellular Endocrinology | volume = 225 | issue = 1–2 | pages = 127–32 | date = October 2004 | pmid = 15451577 | doi = 10.1016/j.mce.2004.07.011 | s2cid = 6943949 }}</ref> and endocrine function. Conversely, inhibin downregulates FSH synthesis and inhibits FSH secretion.<ref>{{cite journal | vauthors = van Zonneveld P, Scheffer GJ, Broekmans FJ, Blankenstein MA, de Jong FH, Looman CW, Habbema JD, te Velde ER | title = Do cycle disturbances explain the age-related decline of female fertility? Cycle characteristics of women aged over 40 years compared with a reference population of young women | journal = Human Reproduction | volume = 18 | issue = 3 | pages = 495–501 | date = March 2003 | pmid = 12615813 | doi = 10.1093/humrep/deg138 | doi-access = free }}</ref> The existence of inhibin was hypothesized as early as 1916; however, it was not demonstrated to exist until Neena Schwartz and Cornelia Channing's work in the mid-1970s, after which both proteins were molecularly characterized ten years later.<ref>{{cite journal | vauthors = Makanji Y, Zhu J, Mishra R, Holmquist C, Wong WP, Schwartz NB, Mayo KE, Woodruff TK | title = Inhibin at 90: from discovery to clinical application, a historical review | journal = Endocrine Reviews | volume = 35 | issue = 5 | pages = 747–94 | date = October 2014 | pmid = 25051334 | doi = 10.1210/er.2014-1003 | pmc=4167436}}</ref>

Activin is a dimer composed of two identical or very similar beta subunits. Inhibin is also a dimer wherein the first component is a beta subunit similar or identical to the beta subunit in activin. However, in contrast to activin, the second component of the inhibin dimer is a more distantly-related alpha subunit.<ref name="pmid3346366">{{cite journal | vauthors = Burger HG, Igarashi M | title = Inhibin: definition and nomenclature, including related substances | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 66 | issue = 4 | pages = 885–6 | date = April 1988 | pmid = 3346366 }}</ref><ref name="pmid15027884">{{cite journal | vauthors = Robertson DM, Burger HG, Fuller PJ | s2cid = 12202820 | title = Inhibin/activin and ovarian cancer | journal = Endocrine-Related Cancer | volume = 11 | issue = 1 | pages = 35–49 | date = March 2004 | pmid = 15027884 | doi = 10.1677/erc.0.0110035 | doi-access = free }}</ref> Activin, inhibin and a number of other structurally related proteins such as anti-Müllerian hormone, bone morphogenetic protein, and growth differentiation factor belong to the TGF-β protein superfamily.<ref name="pmid8299934"/>

== Structure == The activin and inhibin protein complexes are both dimeric in structure, and, in each complex, the two monomers are linked to one another by a single disulfide bond.<ref name="pmid3122219">{{cite journal | vauthors = Ying SY | title = Inhibins and activins: chemical properties and biological activity | journal = Proceedings of the Society for Experimental Biology and Medicine | volume = 186 | issue = 3 | pages = 253–64 | date = December 1987 | pmid = 3122219 | doi = 10.3181/00379727-186-42611a | s2cid = 36872324 }}</ref> In addition, both complexes are derived from the same family of related genes and proteins but differ in their subunit composition.<ref name="pmid3346366"/> Below is a list of the most common inhibin and activin complexes and their subunit composition:

{{col-begin|width=auto}} {{col-break}} {| class="wikitable" border="3" style="text-align:center" |- ! rowspan="2" width="100" | Class ! rowspan="2" width="100" | Activity ! rowspan="2" width="100" | Complex ! colspan="3" | Dimer subunits |- ! width="80" | 1 ! width="80" | 2 |- | rowspan="2" | Inhibin | rowspan="2" | inhibits FSH secretion | Inhibin A | α | βA |- | Inhibin B | α | βB |- | rowspan="3" | Activin | rowspan="3" | stimulates FSH secretion | Activin A | βA | βA |- | Activin AB | βA | βB |- | Activin B | βB | βB |} {{col-break}} thumb|left|330px|Schematic diagram of the 1D structures of inhibin and activin. The black line between the monomers represents a disulfide bond. {{col-end}}

The alpha and beta subunits share approximately 25% sequence similarity, whereas the similarity between beta subunits is approximately 65%.<ref name="pmid8299934">{{cite journal | vauthors = Kingsley DM | title = The TGF-beta superfamily: new members, new receptors, and new genetic tests of function in different organisms | journal = Genes & Development | volume = 8 | issue = 2 | pages = 133–46 | date = Jan 1994 | pmid = 8299934 | doi = 10.1101/gad.8.2.133 | doi-access = free }}</ref>

In mammals, four beta subunits have been described, called activin βA, activin βB, activin βC and activin βE. Activin βA and βB are identical to the two beta subunits of inhibin. A fifth subunit, activin βD, has been described in ''Xenopus laevis''. Two activin βA subunits give rise to activin A, one βA, and one βB subunit gives rise to activin AB, and so on. Various, but not all theoretically possible, heterodimers have been described.<ref name="pmid16973148">{{cite journal | vauthors = Xu P, Hall AK | title = The role of activin in neuropeptide induction and pain sensation | journal = Developmental Biology | volume = 299 | issue = 2 | pages = 303–9 | date = November 2006 | pmid = 16973148 | doi = 10.1016/j.ydbio.2006.08.026 | doi-access = }}</ref><ref name="pmid18350601">{{cite journal|vauthors=Deli A, Kreidl E, Santifaller S, Trotter B, Seir K, Berger W, Schulte-Hermann R, Rodgarkia-Dara C, Grusch M |title=Activins and activin antagonists in hepatocellular carcinoma |journal=World Journal of Gastroenterology |volume=14 |issue=11 |pages=1699–709 |date=March 2008 |pmid=18350601 |pmc=2695910 |doi=10.3748/wjg.14.1699 |doi-access=free }}</ref> The subunits are linked by a single covalent disulfide bond.

The βC subunit is able to form activin heterodimers with βA or βB subunits but is unable to dimerize with inhibin α.<ref name="pmid11134153">{{cite journal | vauthors = Mellor SL, Cranfield M, Ries R, Pedersen J, Cancilla B, de Kretser D, Groome NP, Mason AJ, Risbridger GP | title = 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 | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 85 | issue = 12 | pages = 4851–8 | date = December 2000 | doi = 10.1210/jcem.85.12.7052 | pmid = 11134153 | doi-access = free }}</ref>

== Function == === Activin === Activin is produced in the gonads, pituitary gland, placenta, and other organs: * In the ovarian follicle, activin increases FSH binding and FSH-induced aromatization. It participates in androgen synthesis enhancing LH action in the ovary and testis. In the male, activin enhances spermatogenesis. * Activin is strongly expressed in wounded skin, and overexpression of activin in epidermis of transgenic mice improves wound healing and enhances scar formation. Its action in wound repair and skin morphogenesis is through stimulation of keratinocytes and stromal cells in a dose-dependent manner.<ref name="Bamberger Schärer Antsiferova Tychsen 2021 p. ">{{cite journal | last1=Bamberger | first1=Casimir | last2=Schärer | first2=Agnes | last3=Antsiferova | first3=Maria | last4=Tychsen | first4=Birte | last5=Pankow | first5=Sandra | last6=Müller | first6=Mischa | last7=Rülicke | first7=Thomas | last8=Paus | first8=Ralf | last9=Werner | first9=Sabine | title=Activin Controls Skin Morphogenesis and Wound Repair Predominantly via Stromal Cells and in a Concentration-Dependent Manner via Keratinocytes | journal=The American Journal of Pathology | volume=167 | issue=3 | date=2021-03-09 | pages=733–747 | pmid=16127153 | doi=10.1016/S0002-9440(10)62047-0 | pmc=1698729 }}</ref> * Activin also regulates the morphogenesis of branching organs such as the prostate, lung, and especially kidney. Activin A increased the expression level of type-I collagen suggesting that activin A acts as a potent activator of fibroblasts. * Lack of activin during development results in neural developmental defects. *Upregulation of Activin A drives pluripotent stem cells into a mesoendodermal fate, and thus provides a useful tool for stem cell differentiation and organoid formation.<ref name="pmid25670788">{{cite journal | vauthors = Pauklin S, Vallier L | title = Activin/Nodal signalling in stem cells | journal = Development | volume = 142 | issue = 4 | pages = 607–19 | year = 2015 | pmid = 25670788 | doi = 10.1242/dev.091769 | doi-access = free }}</ref>

=== Inhibin === In both females and males, inhibin inhibits FSH production. Inhibin does not inhibit the secretion of GnRH from the hypothalamus.<ref name="pmid15618291">{{cite journal | vauthors = Luisi S, Florio P, Reis FM, Petraglia F | title = Inhibins in female and male reproductive physiology: role in gametogenesis, conception, implantation and early pregnancy | journal = Human Reproduction Update | volume = 11 | issue = 2 | pages = 123–35 | year = 2005 | pmid = 15618291 | doi = 10.1093/humupd/dmh057 | doi-access = }}</ref><ref>{{cite book |vauthors=Le T, Bhushan V, Hofmann J | title = First Aid for the USMLE Step 1 |url=https://archive.org/details/firstaidforusmle2011leta |url-access=limited | year = 2012 | publisher = McGraw Hill | page = [https://archive.org/details/firstaidforusmle2011leta/page/n585 534] | isbn = 978-0-07-177636-3 }}</ref> However, the overall mechanism differs between the sexes:

==== In females ==== Inhibin is produced in the gonads, pituitary gland, placenta, corpus luteum and other organs.

FSH stimulates the secretion of inhibin from the granulosa cells of the ovarian follicles in the ovaries. In turn, inhibin suppresses FSH. * ''Inhibin B'' reaches a peak in the early- to mid-follicular phase, and a second peak at ovulation. * ''Inhibin A'' reaches its peak in the mid-luteal phase.

Inhibin secretion is diminished by GnRH, and enhanced by insulin-like growth factor-1 (IGF-1).

==== In males ==== It is secreted from the Sertoli cells,<ref>{{cite journal | vauthors = Skinner MK, McLachlan RI, Bremner WJ | title = Stimulation of Sertoli cell inhibin secretion by the testicular paracrine factor PModS | journal = Molecular and Cellular Endocrinology | volume = 66 | issue = 2 | pages = 239–49 | date = October 1989 | pmid = 2515083 | doi = 10.1016/0303-7207(89)90036-1 | hdl = 1773/4395 | s2cid = 21885326 | hdl-access = free }}</ref> located in the seminiferous tubules inside the testes. Androgens stimulate inhibin production; this protein may also help to locally regulate spermatogenesis.<ref>{{cite journal | vauthors = Meachem SJ, Nieschlag E, Simoni M | title = Inhibin B in male reproduction: pathophysiology and clinical relevance | journal = European Journal of Endocrinology| volume = 145 | issue = 5 | pages = 561–71 | date = November 2001 | pmid = 11720872 | doi = 10.1530/eje.0.1450561 | doi-access = free | hdl = 11380/607797 | hdl-access = free }}</ref>

== Mechanism of action == === Activin === As with other members of the superfamily, activins interact with two types of cell surface transmembrane receptors (Types I and II) which have intrinsic serine/threonine kinase activities in their cytoplasmic domains: * Activin type 1 receptors: ACVR1, ACVR1B, ACVR1C * Activin type 2 receptors: ACVR2A, ACVR2B

Activin binds to the Type II receptor and initiates a cascade reaction that leads to the recruitment, phosphorylation, and activation of Type I activin receptor. This then interacts with and then phosphorylates SMAD2 and SMAD3, two of the cytoplasmic SMAD proteins.

Smad3 then translocates to the nucleus and interacts with SMAD4 through multimerization, resulting in their modulation as transcription factor complexes responsible for the expression of a large variety of genes.

=== Inhibin === In contrast to activin, much less is known about the mechanism of action of inhibin, but may involve competing with activin for binding to activin receptors and/or binding to inhibin-specific receptors.<ref name="pmid15027884"/>

== Clinical significance == === Activin === Activin A is more plentiful in the adipose tissue of obese, compared to lean persons.<ref name="pmid20530742" /> Activin A promotes the proliferation of adipocyte progenitor cells, while inhibiting their differentiation into adipocytes.<ref name="pmid20530742">{{cite journal | vauthors=Zaragosi LE, Wdziekonski B, Villageois P, Keophiphath M, Maumus M, Tchkonia T, Bourlier V, Mohsen-Kanson T, Ladoux A, Elabd C, Scheideler M, Trajanoski Z, Takashima Y, Amri EZ, Lacasa D, Sengenes C, Ailhaud G, Clément K, Bouloumie A, Kirkland JL, Dani C | title=Activin a plays a critical role in proliferation and differentiation of human adipose progenitors | journal=Diabetes | volume=59 | issue=10 | pages=2513–2521 | year=2010 | url = http://diabetes.diabetesjournals.org/content/59/10/2513.long |doi = 10.2337/db10-0013 | pmc = 3279533 | pmid= 20530742 }}</ref> Activin A also increases inflammatory cytokines in macrophages.<ref name="pmid20530742" />

A mutation in the gene for the activin receptor ACVR1 results in fibrodysplasia ossificans progressiva, a fatal disease that causes muscle and soft tissue to gradually be replaced by bone tissue.<ref name="ACVR1">{{cite journal | vauthors = Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho TJ, Choi IH, Connor JM, Delai P, Glaser DL, LeMerrer M, Morhart R, Rogers JG, Smith R, Triffitt JT, Urtizberea JA, Zasloff M, Brown MA, Kaplan FS | title = A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva | journal = Nature Genetics | volume = 38 | issue = 5 | pages = 525–527 | date = May 2006 | pmid = 16642017 | doi = 10.1038/ng1783 | s2cid = 41579747 }}</ref> This condition is characterized by the formation of an extra skeleton that produces immobilization and eventually death by suffocation.<ref name="ACVR1" /> The mutation in ACVR1 causes FKBP1A, which normally acts as an antagonist of the receptor and blocks osteogenesis (bone growth), to behave as an agonist of the receptor and to induce hyperactive bone growth.<ref name="ACVR1" /> On 2 September 2015, Regeneron Pharmaceuticals announced that they had developed an antibody for activin A that effectively cures the disease in an animal model of the condition.<ref name="Reuters">{{cite web | url = http://mobile.reuters.com/article/idUSKCN0R222Z20150902 | title = Regeneron scientists discover key to excess bone growth in rare disease | author = Julie Steenhuysen | publisher = Reuters | date = 2 September 2015}}</ref>

Mutations in the ACVR1 gene have also been linked to cancer, especially diffuse intrinsic pontine glioma (DIPG).<ref>{{cite journal | vauthors = Taylor KR, Mackay A, Truffaux N, Butterfield YS, Morozova O, Philippe C, Castel D, Grasso CS, Vinci M, Carvalho D, Carcaboso AM, de Torres C, Cruz O, Mora J, Entz-Werle N, Ingram WJ, Monje M, Hargrave D, Bullock AN, Puget S, Yip S, Jones C, Grill J | title = Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma | journal = Nature Genetics | volume = 46 | issue = 5 | pages = 457–61 | date = May 2014 | pmid = 24705252 | pmc = 4018681 | doi = 10.1038/ng.2925 }}</ref><ref name="urlCure Brain Cancer - News - Multiple Breakthroughs in Childhood Brain Cancer DIPG">{{cite web | url = http://www.curebraincancer.org.au/news/1044/multiple-breakthroughs-in-childhood-brain-cancer | title = Cure Brain Cancer - News - Multiple Breakthroughs in Childhood Brain Cancer DIPG | publisher = Cure Brain Cancer Foundation }}</ref><ref name="pmid24705254">{{cite journal | vauthors = Buczkowicz P, Hoeman C, Rakopoulos P, Pajovic S, Letourneau L, Dzamba M, Morrison A, Lewis P, Bouffet E, Bartels U, Zuccaro J, Agnihotri S, Ryall S, Barszczyk M, Chornenkyy Y, Bourgey M, Bourque G, Montpetit A, Cordero F, Castelo-Branco P, Mangerel J, Tabori U, Ho KC, Huang A, Taylor KR, Mackay A, Bendel AE, Nazarian J, Fangusaro JR, Karajannis MA, Zagzag D, Foreman NK, Donson A, Hegert JV, Smith A, Chan J, Lafay-Cousin L, Dunn S, Hukin J, Dunham C, Scheinemann K, Michaud J, Zelcer S, Ramsay D, Cain J, Brennan C, Souweidane MM, Jones C, Allis CD, Brudno M, Becher O, Hawkins C | title = Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations | journal = Nature Genetics | volume = 46 | issue = 5 | pages = 451–6 | date = May 2014 | pmid = 24705254 | doi = 10.1038/ng.2936 | pmc=3997489}}</ref>

Elevated Activin B levels with normal Activin A levels provided a possible biomarker for myalgic encephalomyelitis/chronic fatigue syndrome.<ref>{{cite journal | vauthors = Lidbury BA, Kita B, Lewis DP, Hayward S, Ludlow H, Hedger MP, de Kretser DM | title = Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study | journal = Journal of Translational Medicine | volume = 15 | issue = 1 | pages = 60 | date = March 2017 | pmid = 28302133 | pmc = 5353946 | doi = 10.1186/s12967-017-1161-4 | doi-access = free }}</ref>

Activin A is overexpressed in many cancers. It was shown to promote tumorigenesis by hampering the adaptive anti-tumor immune response in melanoma.<ref>{{cite journal | vauthors = Donovan P, Dubey OA, Kallioinen S, Rogers KW, Muehlethaler K, Müller P, Rimoldi D, Constam DB | title = Paracrine Activin-A Signaling Promotes Melanoma Growth and Metastasis through Immune Evasion | journal = The Journal of Investigative Dermatology | volume = 137 | issue = 12 | pages = 2578–2587 | date = December 2017 | pmid = 28844941 | doi = 10.1016/j.jid.2017.07.845 | doi-access = free }}</ref>

=== Inhibin === Quantification of inhibin A is part of the prenatal quad screen that can be administered during pregnancy at a gestational age of 16–18 weeks. An elevated inhibin A (along with an increased beta-hCG, decreased AFP, and a decreased estriol) is suggestive of the presence of a fetus with Down syndrome.<ref>{{cite journal | vauthors = Aitken DA, Wallace EM, Crossley JA, Swanston IA, van Pareren Y, van Maarle M, Groome NP, Macri JN, Connor JM | title = Dimeric inhibin A as a marker for Down's syndrome in early pregnancy | journal = The New England Journal of Medicine | volume = 334 | issue = 19 | pages = 1231–6 | date = May 1996 | pmid = 8606718 | doi = 10.1056/NEJM199605093341904 | doi-access = free }}</ref> As a screening test, abnormal quad screen test results need to be followed up with more definitive tests.

It also has been used as a marker for ovarian cancer.<ref>{{cite journal | vauthors = Robertson DM, Pruysers E, Jobling T | title = Inhibin as a diagnostic marker for ovarian cancer | journal = Cancer Letters | volume = 249 | issue = 1 | pages = 14–7 | date = April 2007 | pmid = 17320281 | doi = 10.1016/j.canlet.2006.12.017 }}</ref><ref>{{cite journal | vauthors = Robertson DM, Pruysers E, Burger HG, Jobling T, McNeilage J, Healy D | title = Inhibins and ovarian cancer | journal = Molecular and Cellular Endocrinology | volume = 225 | issue = 1–2 | pages = 65–71 | date = October 2004 | pmid = 15451569 | doi = 10.1016/j.mce.2004.02.014 | s2cid = 33801243 }}</ref>

Inhibin B may be used as a marker of spermatogenesis function and male infertility. The mean serum inhibin B level is significantly higher among fertile men (approximately 140 pg/mL) than in infertile men (approximately 80 pg/mL).<ref>{{cite journal | vauthors = Myers GM, Lambert-Messerlian GM, Sigman M | title = Inhibin B reference data for fertile and infertile men in Northeast America | journal = Fertility and Sterility | volume = 92 | issue = 6 | pages = 1920–3 | date = December 2009 | pmid = 19006797 | doi = 10.1016/j.fertnstert.2008.09.033 | doi-access = free }}</ref> In men with azoospermia, a positive test for inhibin B slightly raises the chances for successfully achieving pregnancy through testicular sperm extraction (TESE), although the association is not very substantial, having a sensitivity of 0.65 (95% confidence interval [CI]: 0.56–0.74) and a specificity of 0.83 (CI: 0.64–0.93) for prediction the presence of sperm in the testes in non-obstructive azoospermia.<ref name="pmid20601364">{{cite journal | vauthors = Toulis KA, Iliadou PK, Venetis CA, Tsametis C, Tarlatzis BC, Papadimas I, Goulis DG | title = Inhibin B and anti-Mullerian hormone as markers of persistent spermatogenesis in men with non-obstructive azoospermia: a meta-analysis of diagnostic accuracy studies | journal = Human Reproduction Update | volume = 16 | issue = 6 | pages = 713–24 | year = 2010 | pmid = 20601364 | doi = 10.1093/humupd/dmq024 | doi-access = free }}</ref>

== References == {{reflist|30em}}

== External links == * {{MeshName|Activin}} * {{MeshName|Inhibin}} * {{cite web | url = http://www.scitopics.com/Activin_and_follistatin_in_liver_biology_and_hepatocellular_carcinoma.html | title = Activin and follistatin in liver biology and hepatocellular carcinoma |vauthors=Grusch M, Kreidl E | date = 2008-08-01 | work = SciTopics | publisher = Elsevier | access-date = 2008-12-24| archive-url= https://web.archive.org/web/20081209123618/http://www.scitopics.com/Activin_and_follistatin_in_liver_biology_and_hepatocellular_carcinoma.html| archive-date= 9 December 2008 | url-status= live}}

{{DEFAULTSORT:Activin And Inhibin}} Category:Mammal reproductive system Category:Hormones of the ovary Category:Peptide hormones Category:TGFβ domain Category:Human female endocrine system