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Mullerian inhibiting substance production and cleavage is modulated by gonadotropins and steroids
Lee Lab Publications
  • Tatsuo Kuroda, Massachusetts General Hospital
  • Mary M. Lee, University of Massachusetts Medical School
  • Richard C. Ragin, Massachusetts General Hospital
  • Seiichi Hirobe, Massachusetts General Hospital
  • Patricia K. Donahoe, Massachusetts General Hospital
UMMS Affiliation
Department of Pediatrics
Document Type
Medical Subject Headings
Amino Acid Sequence; Animals; Anti-Mullerian Hormone; Chorionic Gonadotropin; Estrogens; Female; Follicle Stimulating Hormone; *Glycoproteins; Gonadal Steroid Hormones; Gonadotropins; Growth Inhibitors; Immunoenzyme Techniques; Luteinizing Hormone; Male; Molecular Sequence Data; Peptide Fragments; Pregnancy; Protein Processing, Post-Translational; Rats; Rats, Inbred Strains; Testicular Hormones; Testis; Testosterone
Analysis of the ontogeny and localization of the amino (N)-terminal and carboxy (C)-terminal cleavage products of Mullerian Inhibiting Substance (MIS) and their modulation by hormones of the hypothalamic-pituitary gonadal axis by immunohistochemistry and Northern analysis led to the discovery of a novel mode of posttranslational regulation of this differentiating agent. Antibody to both holo- and C-terminal MIS identically stained the cytosol of testicular Sertoli cells from 21-day fetal rats, whereas staining of antibody to N-terminal MIS localized to the basement membrane of seminiferous tubules. In addition, when studied longitudinally, basement membrane staining for N-terminal MIS persisted; cytosolic staining for C-terminal MIS was no longer detectable in post-natal testes, but marked basement membrane staining for the N-terminal fragment could still be observed in the testes of untreated 7-day postnatal animals. When 19-day fetuses were injected with FSH, testes collected 2 days later showed less immunohistochemical staining for holo-, N-, and C-terminal MIS, and less MIS messenger RNA. This suggested that FSH downregulates MIS transcription, as had been shown previously in neonatal testes treated with FSH. Testes collected at 21 days from fetuses treated at day 19 in utero with human CG or testosterone, also showed less staining for holo-MIS, but, surprisingly, increased staining for the N- and C-terminal fragments. These changes in MIS protein were accompanied by no or minimal changes in MIS messenger RNA levels, indicating that human CG and testosterone do not affect transcription, but may regulate the cleavage and/or dissociation of MIS. This study describes a form of post-translational regulation of MIS and shows that both transcription and processing of MIS may be differentially modulated by gonadotropins and sex steroids.
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Citation: Endocrinology. 1991 Dec;129(6):2985-92. Link to article on publisher's site

At the time of publication, Mary Lee was not yet affiliated with the University of Massachusetts Medical School.

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Link to Article in PubMed
PubMed ID
Citation Information
Tatsuo Kuroda, Mary M. Lee, Richard C. Ragin, Seiichi Hirobe, et al.. "Mullerian inhibiting substance production and cleavage is modulated by gonadotropins and steroids" Vol. 129 Iss. 6 (1991) ISSN: 0013-7227 (Linking)
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