Mullerian inhibiting substance requires its N-terminal domain for maintenance of biological activity, a novel finding within the transforming growth factor-beta superfamily.
Mullerian inhibiting substance (MIS)/anti-Mullerian hormone is a differentiation factor that causes regression of the Mullerian duct in the developing male fetus and an apparent sex reversal of the fetal ovary when inappropriately exposed to it. The purified product is a 140-kilodalton glycoprotein composed of two identical subunits. We show that a C-terminal fragment of MIS, which shares homology with transforming growth factor-beta, causes regression of the Mullerian duct and inhibits the biosynthesis of aromatase in the fetal ovary. However, both activities are enhanced dramatically by addition of the N-terminal portion of MIS. Under conditions where potentiation occurs, the N- and C-terminal domains of MIS reassociate. These results indicate that the N-terminus of MIS, unlike that of the other members of the transforming growth factor-beta family, plays a role in maintaining the biological activity of the C-terminus.
Wilson
C A
CA
Biogen, Inc., Cambridge, Massachusetts 02142.
di Clemente
N
N
Ehrenfels
C
C
Pepinsky
R B
RB
Josso
N
N
Vigier
B
B
Cate
R L
RL
D000818:Animals; D054304:Anti-Mullerian Hormone; D000911:Antibodies, Monoclonal / Q000276:immunology; D001141:Aromatase / Q000096:biosynthesis; D016466:CHO Cells; D002417:Cattle; D006224:Cricetinae; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism; D006023:Glycoproteins; D006131:Growth Inhibitors / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D009095:Mullerian Ducts / Q000187:drug effects*; D005810:Multigene Family; D010053:Ovary / Q000196:embryology / Q000201:enzymology; D010446:Peptide Fragments / Q000494:pharmacology*; D017510:Protein Folding; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013735:Testicular Hormones / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology; D016212:Transforming Growth Factor beta
D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D006131:Growth Inhibitors; D010446:Peptide Fragments; D011994:Recombinant Proteins; D013735:Testicular Hormones; D016212:Transforming Growth Factor beta; D054304:Anti-Mullerian Hormone; D001141:Aromatase; D005341:Fibrinolysin