title: Mullerian inhibiting substance: a gonadal hormone with multiple functions.
abstract: Mullerian inhibiting substance (MIS) is the gonadal hormone that causes regression of the Mullerian ducts, the anlagen of the female internal reproductive structures, during male embryogenesis. MIS is a member of the large transforming growth factor-beta (TGF beta) multigene family of glycoproteins that are involved in the regulation of growth and differentiation. The proteins in this gene family are all produced as dimeric precursors and undergo posttranslational processing for activation, requiring cleavage and dissociation to release bioactive C-terminal fragments. Similarly, the 140 kilodalton (kDa) disulfide-linked homodimer of MIS is proteolytically cleaved to generate its active C-terminal fragments. The sexually dimorphic expression of MIS in Sertoli cells of the testis and granulosa cells of the ovary is critical for normal differentiation of the internal reproductive tract structures. A number of extra-Mullerian functions such as control of germ cell maturation and gonadal morphogenesis, induction of the abdominal phase of testicular descent, suppression of lung maturation, and growth inhibition of transformed cells have also been proposed for this growth-inhibitory hormone and will be discussed. This article will summarize the current understanding of the biology and multiple functions of MIS including its activation, regulation, and mechanism of action and discuss areas of interest in ongoing research.
authors.affiliation: Pediatric Surgical Research Laboratory, Massachusetts General Hospital, Boston 02114.
authors.forename: M M
authors.initials: MM
authors.lastname: Lee
authors.forename: P K
authors.initials: PK
authors.lastname: Donahoe
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D054304:Anti-Mullerian Hormone; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D012734:Disorders of Sex Development / Q000175:diagnosis / Q000209:etiology; D005260:Female; D005786:Gene Expression Regulation; D006023:Glycoproteins; D006066:Gonads / Q000196:embryology; D006131:Growth Inhibitors / Q000097:blood / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008168:Lung / Q000196:embryology; D008297:Male; D008969:Molecular Sequence Data; D009095:Mullerian Ducts / Q000196:embryology; D005810:Multigene Family; D013735:Testicular Hormones / Q000097:blood / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014565:Urogenital Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000473:pathology
chemical_list: D006023:Glycoproteins; D006131:Growth Inhibitors; D013735:Testicular Hormones; D054304:Anti-Mullerian Hormone