Most Cleaved Anti-Müllerian Hormone Binds Its Receptor in Human Follicular Fluid but Little Is Competent in Serum.
Anti-Müllerian hormone (AMH) is an important clinical marker for diagnosing and assessing the reproductive status and/or disorders in men and women. Most studies have not distinguished between levels of inactive AMH precursor and the cleaved noncovalent complex that binds the AMH type II receptor (AMHRII) and initiates signaling.



The objective of the study was to measure the levels of AMH cleavage and bioactivity in human body fluids.



AMH cleavage levels and bioactivity were measured in the serum of six boys and in the follicular fluid and serum of nine control women and 13 women with the polycystic ovary syndrome (PCOS).



AMH cleavage levels were measured by capturing AMH with an anti-AMH antibody, followed by Western blotting. The bioactivity of cleaved AMH was assessed with an ELISA that measures the levels of AMH capable of binding AMHRII.



PCOS women have an elevated level of AMH cleavage in their follicular fluid (24% vs 8% in control women), and most of the cleaved AMH can bind AMHRII. Higher levels of cleavage are observed in female (60%) and male (79%) serum, but very little of the cleaved AMH can bind AMHRII.



These results support an autocrine role for AMH in the pathophysiology of PCOS in the follicle. In addition, they indicate that AMH undergoes interactions or structural changes after cleavage that prevent receptor binding, meaning, unexpectedly, that the level of cleaved AMH in biological fluids does not always reflect the level of bioactive AMH.
Université Paris Diderot (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Sorbonne Paris Cité, F-75013 Paris, France; Institut National de la Santé et de la Recherche Médicale Unité 1133 (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Physiologie de l'Axe Gonadotrope, F-75013 Paris, France; Centre National de la Recherche Scientifique (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Unité Mixte de Recherche 8251, Biologie Fonctionnelle et Adaptative, F-75013 Paris, France; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (R.R.), Consejo Nacional de Investigaciones Cientificas y Técnicas-FEI, División de Endocrinología, Hospital de Niños R Gutiérrez, C1425EFD Buenos Aires, Argentina; Biogen (P.C., R.B.P.), Cambridge, Massachusetts 02142; and Department of Chemistry (R.L.C.), Boston University, Boston, Massachusetts 02215.
Alice
A
Pierre
Université Paris Diderot (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Sorbonne Paris Cité, F-75013 Paris, France; Institut National de la Santé et de la Recherche Médicale Unité 1133 (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Physiologie de l'Axe Gonadotrope, F-75013 Paris, France; Centre National de la Recherche Scientifique (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Unité Mixte de Recherche 8251, Biologie Fonctionnelle et Adaptative, F-75013 Paris, France; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (R.R.), Consejo Nacional de Investigaciones Cientificas y Técnicas-FEI, División de Endocrinología, Hospital de Niños R Gutiérrez, C1425EFD Buenos Aires, Argentina; Biogen (P.C., R.B.P.), Cambridge, Massachusetts 02142; and Department of Chemistry (R.L.C.), Boston University, Boston, Massachusetts 02215.
Chrystèle
C
Racine
Université Paris Diderot (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Sorbonne Paris Cité, F-75013 Paris, France; Institut National de la Santé et de la Recherche Médicale Unité 1133 (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Physiologie de l'Axe Gonadotrope, F-75013 Paris, France; Centre National de la Recherche Scientifique (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Unité Mixte de Recherche 8251, Biologie Fonctionnelle et Adaptative, F-75013 Paris, France; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (R.R.), Consejo Nacional de Investigaciones Cientificas y Técnicas-FEI, División de Endocrinología, Hospital de Niños R Gutiérrez, C1425EFD Buenos Aires, Argentina; Biogen (P.C., R.B.P.), Cambridge, Massachusetts 02142; and Department of Chemistry (R.L.C.), Boston University, Boston, Massachusetts 02215.
Rodolfo A
RA
Rey
Université Paris Diderot (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Sorbonne Paris Cité, F-75013 Paris, France; Institut National de la Santé et de la Recherche Médicale Unité 1133 (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Physiologie de l'Axe Gonadotrope, F-75013 Paris, France; Centre National de la Recherche Scientifique (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Unité Mixte de Recherche 8251, Biologie Fonctionnelle et Adaptative, F-75013 Paris, France; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (R.R.), Consejo Nacional de Investigaciones Cientificas y Técnicas-FEI, División de Endocrinología, Hospital de Niños R Gutiérrez, C1425EFD Buenos Aires, Argentina; Biogen (P.C., R.B.P.), Cambridge, Massachusetts 02142; and Department of Chemistry (R.L.C.), Boston University, Boston, Massachusetts 02215.
Renato
R
Fanchin
Université Paris Diderot (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Sorbonne Paris Cité, F-75013 Paris, France; Institut National de la Santé et de la Recherche Médicale Unité 1133 (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Physiologie de l'Axe Gonadotrope, F-75013 Paris, France; Centre National de la Recherche Scientifique (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Unité Mixte de Recherche 8251, Biologie Fonctionnelle et Adaptative, F-75013 Paris, France; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (R.R.), Consejo Nacional de Investigaciones Cientificas y Técnicas-FEI, División de Endocrinología, Hospital de Niños R Gutiérrez, C1425EFD Buenos Aires, Argentina; Biogen (P.C., R.B.P.), Cambridge, Massachusetts 02142; and Department of Chemistry (R.L.C.), Boston University, Boston, Massachusetts 02215.
Joëlle
J
Taieb
Université Paris Diderot (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Sorbonne Paris Cité, F-75013 Paris, France; Institut National de la Santé et de la Recherche Médicale Unité 1133 (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Physiologie de l'Axe Gonadotrope, F-75013 Paris, France; Centre National de la Recherche Scientifique (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Unité Mixte de Recherche 8251, Biologie Fonctionnelle et Adaptative, F-75013 Paris, France; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (R.R.), Consejo Nacional de Investigaciones Cientificas y Técnicas-FEI, División de Endocrinología, Hospital de Niños R Gutiérrez, C1425EFD Buenos Aires, Argentina; Biogen (P.C., R.B.P.), Cambridge, Massachusetts 02142; and Department of Chemistry (R.L.C.), Boston University, Boston, Massachusetts 02215.
Joëlle
J
Cohen-Tannoudji
Université Paris Diderot (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Sorbonne Paris Cité, F-75013 Paris, France; Institut National de la Santé et de la Recherche Médicale Unité 1133 (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Physiologie de l'Axe Gonadotrope, F-75013 Paris, France; Centre National de la Recherche Scientifique (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Unité Mixte de Recherche 8251, Biologie Fonctionnelle et Adaptative, F-75013 Paris, France; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (R.R.), Consejo Nacional de Investigaciones Cientificas y Técnicas-FEI, División de Endocrinología, Hospital de Niños R Gutiérrez, C1425EFD Buenos Aires, Argentina; Biogen (P.C., R.B.P.), Cambridge, Massachusetts 02142; and Department of Chemistry (R.L.C.), Boston University, Boston, Massachusetts 02215.
Paul
P
Carmillo
Université Paris Diderot (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Sorbonne Paris Cité, F-75013 Paris, France; Institut National de la Santé et de la Recherche Médicale Unité 1133 (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Physiologie de l'Axe Gonadotrope, F-75013 Paris, France; Centre National de la Recherche Scientifique (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Unité Mixte de Recherche 8251, Biologie Fonctionnelle et Adaptative, F-75013 Paris, France; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (R.R.), Consejo Nacional de Investigaciones Cientificas y Técnicas-FEI, División de Endocrinología, Hospital de Niños R Gutiérrez, C1425EFD Buenos Aires, Argentina; Biogen (P.C., R.B.P.), Cambridge, Massachusetts 02142; and Department of Chemistry (R.L.C.), Boston University, Boston, Massachusetts 02215.
R Blake
RB
Pepinsky
Université Paris Diderot (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Sorbonne Paris Cité, F-75013 Paris, France; Institut National de la Santé et de la Recherche Médicale Unité 1133 (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Physiologie de l'Axe Gonadotrope, F-75013 Paris, France; Centre National de la Recherche Scientifique (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Unité Mixte de Recherche 8251, Biologie Fonctionnelle et Adaptative, F-75013 Paris, France; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (R.R.), Consejo Nacional de Investigaciones Cientificas y Técnicas-FEI, División de Endocrinología, Hospital de Niños R Gutiérrez, C1425EFD Buenos Aires, Argentina; Biogen (P.C., R.B.P.), Cambridge, Massachusetts 02142; and Department of Chemistry (R.L.C.), Boston University, Boston, Massachusetts 02215.
Richard L
RL
Cate
Université Paris Diderot (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Sorbonne Paris Cité, F-75013 Paris, France; Institut National de la Santé et de la Recherche Médicale Unité 1133 (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Physiologie de l'Axe Gonadotrope, F-75013 Paris, France; Centre National de la Recherche Scientifique (A.P., C.R., R.F., J.T., J.C.-T., R.L.C., N.d.C.), Unité Mixte de Recherche 8251, Biologie Fonctionnelle et Adaptative, F-75013 Paris, France; Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (R.R.), Consejo Nacional de Investigaciones Cientificas y Técnicas-FEI, División de Endocrinología, Hospital de Niños R Gutiérrez, C1425EFD Buenos Aires, Argentina; Biogen (P.C., R.B.P.), Cambridge, Massachusetts 02142; and Department of Chemistry (R.L.C.), Boston University, Boston, Massachusetts 02215.
Nathalie
N
di Clemente
D000328:Adult; D054304:Anti-Mullerian Hormone / Q000097:blood / Q000378:metabolism*; D002648:Child; D005260:Female; D015571:Follicular Fluid / Q000378:metabolism*; D006801:Humans; D008297:Male; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000378:metabolism*; D011485:Protein Binding; D018000:Receptors, Peptide / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*
D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; C084621:anti-Mullerian hormone receptor; D054304:Anti-Mullerian Hormone