INHBB explained

Inhibin, beta B, also known as INHBB, is a protein which in humans is encoded by the INHBB gene.^{[1] [2]} INHBB is a subunit of both activin and inhibin, two closely related glycoproteins with opposing biological effects.

Function

Inhibin

Inhibins are heterodimeric glycoproteins composed of an α subunit (INHA) and one of two homologous, but distinct, β subunits (βA or βB, this protein). mRNA for the two subunits has been demonstrated in the testes of adult rats.^[3] Inhibin can bind specifically to testicular interstitial cells throughout development and may be an important regulator of Leydig cell testosterone production or interstitial cell function.^[4]

The inhibin beta B subunit joins the α subunit to form a pituitary FSH secretion inhibitor. Inhibin has been shown to regulate gonadal stromal cell proliferation negatively and to have tumour-suppressor activity. In addition, serum levels of inhibin have been shown to reflect the size of granulosa-cell tumors and can therefore be used as a marker for primary as well as recurrent disease. Because expression in gonadal and various extragonadal tissues may vary severalfold in a tissue-specific fashion, it is proposed that inhibin may be both a growth/differentiation factor and a hormone.

Activin

Furthermore, the beta B subunit forms a homodimer, activin B, and also joins with the beta A subunit to form a heterodimer, activin AB, both of which stimulate FSH secretion.^[2]

Tissue distribution

Sections of testicular tissue from rat revealed positive immunoreactivity against anti-inhibin intensely appeared in Leydig cells. In adult animals, binding of ¹²⁵I inhibin was localized primarily to the interstitial compartment of the testis.^[4] Also, Jin et al., (2001) reported that Leydig cells showed strong positive staining for the inhibin βA subunit in pigs testis.^[5]

Receptors

In situ ligand binding studies have shown that ¹²⁵I inhibin βA binds specifically to Leydig cells throughout rat testis development. These results suggest that inhibin has been considered as a regulator of Leydig cell differentiated function.^{[6] [7]} Recently, additional inhibin specific binding proteins were identified in inhibin target tissues, including pituitary and Leydig cells.^{[8] [9]} From these receptors betaglycan (the TGF-β type III receptor) and InhBP/p120 (a membrane-tethered proteoglycan) were identified as putative inhibin receptors and they are all present in Leydig cells. However, a faint positive reaction was detected in Leydig cell cytoplasm in rats treated with anise oil.^[10] This may be related to the damaged Leydig cells, as a result of the decreasing of inhibin expression. This may be related to its content of safrole.

Cancer

INHBB gene has been observed progressively downregulated in Human papillomavirus-positive neoplastic keratinocytes derived from uterine cervical preneoplastic lesions at different levels of malignancy. ^[11] For this reason, INHBB is likely to be associated with tumorigenesis and may be a potential prognostic marker for uterine cervical preneoplastic lesions progression. ^[11]

Further reading

• Ying SY . Inhibins and activins: chemical properties and biological activity. . Proc. Soc. Exp. Biol. Med. . 186 . 3 . 253–64 . 1988 . 3122219 . 10.3181/00379727-186-42611a. 36872324 .
• Munz B, Hübner G, Tretter Y, etal . A novel role of activin in inflammation and repair. . J. Endocrinol. . 161 . 2 . 187–93 . 1999 . 10320815 . 10.1677/joe.0.1610187 . free .
• Welt CK . The physiology and pathophysiology of inhibin, activin and follistatin in female reproduction. . Curr. Opin. Obstet. Gynecol. . 14 . 3 . 317–23 . 2002 . 12032389 . 10.1097/00001703-200206000-00012 . 44327401 .
• Shav-Tal Y, Zipori D . The role of activin a in regulation of hemopoiesis. . Stem Cells . 20 . 6 . 493–500 . 2003 . 12456957 . 10.1634/stemcells.20-6-493 . 36242096 . free .
• Lahlou N, Roger M . Inhibin B in pubertal development and pubertal disorders. . Semin. Reprod. Med. . 22 . 3 . 165–75 . 2005 . 15319819 . 10.1055/s-2004-831892 . 260317318 .
• Mathews LS, Vale WW . Expression cloning of an activin receptor, a predicted transmembrane serine kinase. . Cell . 65 . 6 . 973–82 . 1991 . 1646080 . 10.1016/0092-8674(91)90549-E . 36407277 .
• Schmelzer CH, Burton LE, Tamony CM, etal . Purification and characterization of recombinant human activin B. . Biochim. Biophys. Acta . 1039 . 2 . 135–41 . 1990 . 2364091 . 10.1016/0167-4838(90)90178-I .
• Mason AJ, Berkemeier LM, Schmelzer CH, Schwall RH . Activin B: precursor sequences, genomic structure and in vitro activities . Mol. Endocrinol. . 3 . 9 . 1352–8 . 1990 . 2575216 . 10.1210/mend-3-9-1352 . 3856861 . free .
• Feng ZM, Bardin CW, Chen CL . Characterization and regulation of testicular inhibin beta-subunit mRNA . Mol. Endocrinol. . 3 . 6 . 939–48 . 1989 . 2739657 . 10.1210/mend-3-6-939 . free .
• Barton DE, Yang-Feng TL, Mason AJ, etal . Mapping of genes for inhibin subunits alpha, beta A, and beta B on human and mouse chromosomes and studies of jsd mice . Genomics . 5 . 1 . 91–9 . 1989 . 2767687 . 10.1016/0888-7543(89)90091-8 . free .
• Burger HG, Igarashi M . Inhibin: definition and nomenclature, including related substances . Endocrinology . 122 . 4 . 1701–2 . 1988 . 3345731 . 10.1210/endo-122-4-1701 .
• Mason AJ, Niall HD, Seeburg PH . Structure of two human ovarian inhibins . Biochem. Biophys. Res. Commun. . 135 . 3 . 957–64 . 1986 . 3754442 . 10.1016/0006-291X(86)91021-1 .
• Martens JW, de Winter JP, Timmerman MA, etal . Inhibin interferes with activin signaling at the level of the activin receptor complex in Chinese hamster ovary cells . Endocrinology . 138 . 7 . 2928–36 . 1997 . 9202237 . 10.1210/endo.138.7.5250 . free .
• Mellor SL, Cranfield M, Ries R, etal . 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 . J. Clin. Endocrinol. Metab. . 85 . 12 . 4851–8 . 2001 . 10.1210/jcem.85.12.7052 . 11134153 . 15930364 . https://web.archive.org/web/20190224191602/http://pdfs.semanticscholar.org/5cd5/6918dc10f60a98e6560d8cf153706d93fb6d.pdf . dead . 2019-02-24 .
• Chapman SC, Woodruff TK . Modulation of activin signal transduction by inhibin B and inhibin-binding protein (INhBP) . Mol. Endocrinol. . 15 . 4 . 668–79 . 2001 . 11266516 . 10.1210/mend.15.4.0616 . free .
• Salmenkivi K, Arola J, Voutilainen R, etal . Inhibin/activin betaB-subunit expression in pheochromocytomas favors benign diagnosis . J. Clin. Endocrinol. Metab. . 86 . 5 . 2231–5 . 2001 . 10.1210/jcem.86.5.7446 . 11344232 .
• Bahathiq AO, Stewart RL, Wells M, etal . Production of activins by the human endosalpinx . J. Clin. Endocrinol. Metab. . 87 . 11 . 5283–9 . 2002 . 12414903 . 10.1210/jc.2001-011884 . free .

Notes and References

1. Burger HG, Igarashi M . Inhibin: definition and nomenclature, including related substances . Endocrinology . 122 . 4 . 1701–2 . April 1988 . 3345731 . 10.1210/endo-122-4-1701.
2. Web site: Entrez Gene: INHBB inhibin, beta B (activin AB beta polypeptide).
3. Feng ZM, Bardin CW, Chen CL . Characterization and regulation of testicular inhibin beta-subunit mRNA . Mol. Endocrinol. . 3 . 6 . 939–48 . June 1989 . 2739657 . 10.1210/mend-3-6-939. free .
4. Krummen LA, Moore A, Woodruff TK, Covello R, Taylor R, Working P, Mather JP . Localization of inhibin and activin binding sites in the testis during development by in situ ligand binding . Biol. Reprod. . 50 . 4 . 734–44 . April 1994 . 8199254 . 10.1095/biolreprod50.4.734 . free .
5. Jin W, Arai KY, Herath CB, Kondo M, Ishi H, Tanioka Y, Watanabe G, Groome NP, Taya K . Inhibins in the male Göttingen miniature pig: Leydig cells are the predominant source of inhibin B . J. Androl. . 22 . 6 . 953–60 . 2001 . 11700859 . 10.1002/j.1939-4640.2001.tb03435.x . free .
6. Lejeune H, Chuzel F, Sanchez P, Durand P, Mather JP, Saez JM . Stimulating effect of both human recombinant inhibin A and activin A on immature porcine Leydig cell functions in vitro . Endocrinology . 138 . 11 . 4783–91 . November 1997 . 10.1210/endo.138.11.5542 . 9348206 . free .
7. Pierson TM, Wang Y, DeMayo FJ, Matzuk MM, Tsai SY, Omalley BW . Regulable expression of inhibin A in wild-type and inhibin alpha null mice . Mol. Endocrinol. . 14 . 7 . 1075–85 . July 2000 . 10.1210/mend.14.7.0478 . 10894156 . 86195240 . free .
8. Chong H, Pangas SA, Bernard DJ, Wang E, Gitch J, Chen W, Draper LB, Cox ET, Woodruff TK . Structure and expression of a membrane component of the inhibin receptor system . Endocrinology . 141 . 7 . 2600–7 . July 2000 . 10875264 . 10.1210/endo.141.7.7540 . free .
9. Bernard DJ, Chapman SC, Woodruff TK . Inhibin binding protein (InhBP/p120), betaglycan, and the continuing search for the inhibin receptor . Mol. Endocrinol. . 16 . 2 . 207–12 . February 2002 . 11818494 . 10.1210/mend.16.2.0783 . free .
10. Ibrahim . A.A.E.M . 2008 . Correlation between fennel-or anise-oil administration and damage to the testis of adult rats . Egyptian Journal of Biology . 10 . 62–76 .
11. Rotondo JC, Bosi S, Bassi C, Ferracin M, Lanza G, Gafà R, Magri E, Selvatici R, Torresani S, Marci R, Garutti P, Negrini M, Tognon M, Martini F . Gene expression changes in progression of cervical neoplasia revealed by microarray analysis of cervical neoplastic keratinocytes. . J Cell Physiol . 230. 4 . 802–812 . April 2015 . 25205602 . 10.1002/jcp.24808. 11392/2066612 . 24986454 . free .