Anti-Mullerian Hormone (Formerly Mullerian Inhibiting Substance)

2007
Mullerian Inhibiting Substance (Mullerian Inhibiting Hormone)
A peptide growth factor which is a member of the TGFβ family which was originally described as a large glycoprotein secreted by neonatal/fetal testis responsible for regression of the Mullerian Duct during the process of sexual differentiation. See Budzik, G.P., Powell, S.M., Kamagata, S. and Donahoe, P.K., Mullerian inhibiting substance fractionation of dye affinity chromatography, Cell 34, 307-314, 1983; Visser, J.A., Themmen, A.P.N., Anti-Müllerian hormone and folliculogenesis, Molec.Cell.Endocrinol. 234, 81-86, 2005.


2018
Müllerian Inhibiting Substance (Anti-Müllernian Hormone)
Müllerian Inhibiting Substance (MIS), better known today as Anti-Müllernian Hormone (AMH), is a 140 kDa homeodimeric peptide hormone(1) which is processed by limited proteolysis (cleavage between R427 and S428)  to yield a 25 kDa fragment which is the biologically active form with homology to the TGF-β family (2,3).   AMH (Anti-Mullerian hormone is the preferred nomenclature) inhibits the development of uterus and fallopian tubes; the lack of AMH permits the development of these structures as well as other aspects of female reproductive system (4).  AMH have other functions during the female reproductive cycle in the adult (5 ).  Blood  levels in males are high in males in childhood and decrease at puberty.  AMH levels in females are low or absent at birth, variable until 4 years, then increasing until 8 years and remaining constant at levels similar to the male during the reproductive years decreasing after menopause  (6).  AMH was observed to inhibit the growth of ovarian cancer cells (7). There have efforts to use AMH as a therapeutic for ovarian cancer (8-10).  A MAB-based therapeutic is also be being evaluated (11).

References

1. Lane, A.H. and Donahoe, P.K., New insights into Mullerian inhibiting substance and its mechanism of action, J.Endocrinol. 158, 1-6, 1998.
2.  Cate, R.L., Mattallano, R.J., Hessions, C., et al., Isolation of the bovine and human genes for Müllerian inhibiting substance and expression of the human gene in animal cells, Cell 45, 685-698, 1986.
3. Pepinsky, R.B., Sinclair, L.K., Chow, E.P., et al., Proteolytic processing of Mullerian inhibiting substance produces a transforming growth factor-β-like fragment, J.Biol.Chem. 263, 18961-18964, 1988.
4.  Shahrokhi, S.Z., Kazerouni, F., and Ghaffari, F., Anti-Müllerian hormone: genetic and environmental effects,  Clin.Chim.Acta 476, 123-129, 2018).
5.  Dewailly, D., Andersen, C.Y., Balen, A., et al., The  physiology and clinical utility of anti-Mullerian hormone in women, Hum.Reprod.Update 20, 370-385, 2014.
6.  Wong, R.R.Y., Worley, M.J., Jr., Chung, T.K.H., and Wong, Y.F., An update on Müllerian -inhibiting substance: its potential application against ovarian cancer, Endocr.Relat.Cancer 21, R227-R33, 2014.
7.   Masiakos, P.T., MacLaughlin, D.T. Maheswaran, S., et al., Human ovarian cancer cell lines, and primary ascites cells express the human Mullerian inhibiting substance (MIS) type II receptor, bind, and are responsive to MIS, Clin.Cancer Res. 5, 3488-3499, 1999.
8.  ) Kim, J.H., MacLaughlin, D.T., and Donahoe, P.K., Mullerian inhibitory substance/anti-Müllerian hormone: a novel treatment for gynecological tumors, Obstet.Gynecol.Sci. 57, 343-357, 2014.
9.  Pépin, D., Sosulski, A.,  Zhang, L., et al., AAV9 delivering a modified human Mullerian inhibiting substance as a gene therapy in patient-derived  xenografts of ovarian cancer, Proc.Natl.Acad.Sci.USA 112, E4418-E4427, 2015.
10.  Kushnir, V.A., Seifer,D.B., Barad, D.H., Sen, A., and Gleicher, N., Potential therapeutic applications of human anti-Müllerian hormone (AMH) analogues in reproductive medicine, J.Assist.Reprod.Genet. 34, 1105-1113, 2017.
11.  Bougherara, H., Némati, F.,Nicolas, A., et al., The humanized anti-human AMHRII mAb 3C23K exerts an anti-tumor activity against human ovarian cancer through tumor-associated macrophages, Oncotarget 8, 99950-99965, 2017.

© Roger L Lundblad August 4, 2018