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Activin and inhibin: Wikis


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inhibin, alpha
Symbol INHA
Entrez 3623
HUGO 6065
OMIM 147380
RefSeq NM_002191
UniProt P05111
Other data
Locus Chr. 2 q33-qter
inhibin, beta A
The Activin dimer, from 2ARV.pdb
Symbol INHBA
Alt. symbols activin A
Entrez 3624
HUGO 6066
OMIM 147290
RefSeq NM_002192
UniProt P08476
Other data
Locus Chr. 7 p15-p13
inhibin, beta B
Symbol INHBB
Alt. symbols activin B
Entrez 3625
HUGO 6067
OMIM 147390
RefSeq NM_002193
UniProt P09529
Other data
Locus Chr. 2 cen-q13
inhibin, beta C
Symbol INHBC
Alt. symbols activin C
Entrez 3626
HUGO 6068
OMIM 601233
RefSeq NM_005538
UniProt P55103
Other data
Locus Chr. 12 q13
inhibin, beta E
Symbol INHBE
Alt. symbols activin E
Entrez 83729
HUGO 24029
OMIM 612031
RefSeq NM_031479
UniProt P58166
Other data
Locus Chr. 12 q13.2

Activin and inhibin are two closely related protein complexes that have opposing biological effects. 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,[1] metabolism, homeostasis, immune response, wound repair,[2] and endocrine function. Conversely inhibin down regulates FSH synthesis and inhibits FSH secretion.[3]

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.[4][5] 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.[6]



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.[7] In addition, both complexes are derived from the same family of related genes and proteins but differ in their subunit composition.[4] Below is a list of the most common inhibin and activin complexes and their subunit composition:

Class Activity Complex Dimer subunits
1 2
Inhibin inhibits FSH secretion Inhibin A α βA
Inhibin B α βB
Activin stimulates FSH secretion Activin A βA βA
Activin AB βA βB
Activin B βB βB
Schematic diagram of the 1D structures of inhibin and activin. The black line between the monomers represents a disulfide bond.

The alpha and beta subunits share approximately 25% sequence similarity, whereas the similarity between beta subunits is approximately 65%.[6]

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.[8][9] 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.[10]



Activin is produced in the gonads, pituitary gland, placenta, and other organs:


In both females and males, inhibin inhibits FSH production and GnRH release from the hypothalamus. However, the overall mechanism differs between the genders:

In females

In women, FSH stimulates the secretion of inhibin from the granulosa cells of the ovarian follicles in the ovaries. In turn, inhibin suppresses FSH.

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

Inhibin is produced in the gonads, pituitary gland, placenta and other organs.

In males

In men, it is a hormone that inhibits FSH by negative feedback. It is secreted from the Sertoli cells,[12] located in the seminiferous tubules inside the testes. Androgens stimulate inhibin production; this peptide may also help to locally regulate spermatogenesis.

Mechanism of action


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 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.


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.[5]

Clinical significance

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.[13] 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.[14][15]

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).[16]


  1. ^ Chen YG, Wang Q, Lin SL, Chang CD, Chuang J, Chung J, Ying SY (May 2006). "Activin signaling and its role in regulation of cell proliferation, apoptosis, and carcinogenesis". Exp. Biol. Med. (Maywood) 231 (5): 534–44. PMID 16636301.  
  2. ^ Sulyok S, Wankell M, Alzheimer C, Werner S (October 2004). "Activin: an important regulator of wound repair, fibrosis, and neuroprotection". Mol. Cell. Endocrinol. 225 (1-2): 127–32. doi:10.1016/j.mce.2004.07.011. PMID 15451577.  
  3. ^ van Zonneveld P, Scheffer G, Broekmans F, Blankenstein M, de Jong F, Looman C, Habbema J, te Velde E (2003). "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". Hum Reprod 18 (3): 495–501. doi:10.1093/humrep/deg138. PMID 12615813.  
  4. ^ a b Burger HG, Igarashi M (April 1988). "Inhibin: definition and nomenclature, including related substances". The Journal of Clinical Endocrinology and Metabolism 66 (4): 885–6. PMID 3346366.  
  5. ^ a b Robertson DM, Burger HG, Fuller PJ (March 2004). "Inhibin/activin and ovarian cancer". Endocrine-related Cancer 11 (1): 35–49. doi:10.1677/erc.0.0110035. PMID 15027884.  
  6. ^ a b Kingsley DM (January 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.  
  7. ^ Ying SY (December 1987). "Inhibins and activins: chemical properties and biological activity". Proc. Soc. Exp. Biol. Med. 186 (3): 253–64. PMID 3122219.  
  8. ^ Xu P, Hall AK (November 2006). "The role of activin in neuropeptide induction and pain sensation". Dev. Biol. 299 (2): 303–9. doi:10.1016/j.ydbio.2006.08.026. PMID 16973148.  
  9. ^ Deli A, Kreidl E, Santifaller S, Trotter B, Seir K, Berger W, Schulte-Hermann R, Rodgarkia-Dara C, Grusch M (March 2008). "Activins and activin antagonists in hepatocellular carcinoma". World J. Gastroenterol. 14 (11): 1699–709. PMID 18350601.  
  10. ^ Mellor SL, Cranfield M, Ries R, Pedersen J, Cancilla B, de Kretser D, Groome NP, Mason AJ, Risbridger GP (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/jc.85.12.4851. PMID 11134153.  
  11. ^ Bamberger C, Schärer A, Antsiferova M, Tychsen B, Pankow S, Müller M, Rülicke T, Paus R, Werner S (September 2005). "Activin controls skin morphogenesis and wound repair predominantly via stromal cells and in a concentration-dependent manner via keratinocytes". Am. J. Pathol. 167 (3): 733–47. PMID 16127153. PMC 1698729.  
  12. ^ Skinner M, McLachlan R, Bremner W (1989). "Stimulation of Sertoli cell inhibin secretion by the testicular paracrine factor PModS". Mol Cell Endocrinol 66 (2): 239–49. doi:10.1016/0303-7207(89)90036-1. PMID 2515083.  
  13. ^ Aitken D, Wallace E, Crossley J, Swanston I, van Pareren Y, van Maarle M, Groome N, Macri J, Connor J (1996). "Dimeric inhibin A as a marker for Down syndrome in early pregnancy". N Engl J Med 334 (19): 1231–6. doi:10.1056/NEJM199605093341904. PMID 8606718.  
  14. ^ Robertson D, Pruysers E, Jobling T. "Inhibin as a diagnostic marker for ovarian cancer". Cancer Lett. PMID 17320281.  
  15. ^ Robertson D, Pruysers E, Burger H, Jobling T, McNeilage J, Healy D (2004). "Inhibins and ovarian cancer". Mol Cell Endocrinol 225 (1-2): 65–71. doi:10.1016/j.mce.2004.02.014. PMID 15451569.  
  16. ^ Myers GM, Lambert-Messerlian GM, Sigman M (November 2008). "Inhibin B reference data for fertile and infertile men in Northeast America". Fertil. Steril.. doi:10.1016/j.fertnstert.2008.09.033. PMID 19006797.  

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