title: Human blood contains both the uncleaved precursor of anti-Mullerian hormone and a complex of the NH2- and COOH-terminal peptides.
abstract: Anti-Müllerian hormone (AMH) in blood is a marker of ovarian status in women and the presence of cryptic testes in babies. Despite this, the molecular form of AMH in blood has not been verified. AMH is synthesized as an inert proprotein precursor (proAMH), which can be cleaved to yield NH2-terminal (AMHN) and COOH-terminal (AMHC) fragments, that can complex noncovalently (AMHN,C). Developing males have 10-fold more AMH than young adults. We report here that human blood is a mixture of inactive proAMH and receptor-binding AMHN,C. The AMH in the blood of boys, men, and premenopausal women was immunoprecipitated using antibodies to the NH2- and COOH-terminal peptides. The precipitated proteins were then analyzed by Western blots, using recombinant proteins as markers. The glycosylation status of AMH was verified using deglycosylating enzymes. The NH2-terminal antibody precipitated a major protein that migrated alongside rhproAMH and was detected by anti-AMHN and anti-AMHC. This antibody also precipitated significant levels of AMHN and AMHC from all participants. Antibodies specific to AMHC precipitated rhAMHC but did not precipitate AMHC from human blood. Hence, all the AMHC in human blood appears to be bound to AMHN. Both AMHN and proAMH were glycosylated, independent of age and sex. In conclusion, boys and young adults have the same form of AMH, with a significant proportion being the inactive precursor. This raises the possibility that the endocrine functions of AMH are partly controlled by its cleavage in the target organ. The presence of proAMH in blood may confound the use of AMH for diagnosis.
authors.affiliation: Department of Anatomy, Otago School of Medical Sciences and the Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Pankhurst
authors.forename: Ian S
authors.initials: IS
authors.lastname: McLennan
mesh_terms: D000328:Adult; D054304:Anti-Mullerian Hormone / Q000097:blood* / Q000737:chemistry; D002675:Child, Preschool; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D046912:Multiprotein Complexes / Q000097:blood / Q000737:chemistry; D010446:Peptide Fragments / Q000097:blood* / Q000737:chemistry; D011485:Protein Binding; D011498:Protein Precursors / Q000097:blood / Q000737:chemistry; D017434:Protein Structure, Tertiary; D055815:Young Adult
chemical_list: D046912:Multiprotein Complexes; D010446:Peptide Fragments; D011498:Protein Precursors; D054304:Anti-Mullerian Hormone
keywords: amino- and carboxy-terminal anti-Müllerian hormone; anti-Müllerian hormone enzyme-linked immunosorbent assay; boys; furin; menopause; ovarian reserve; pro-anti-Müllerian hormone; sex