Müllerian inhibiting substance production and cleavage is modulated by gonadotropins and steroids

Tatsuo Kuroda, Mary M. Lee, Richard C. Ragin, Seiichi Hirobe, Patricia K. Donahoe

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Analysis of the ontogeny and localization of the amino (N)-terminal and carboxy (C)-terminal cleavage products of Müllerian 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 postnatal 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.

Original languageEnglish
Pages (from-to)2985-2992
Number of pages8
JournalEndocrinology
Volume129
Issue number6
Publication statusPublished - 1991 Dec
Externally publishedYes

Fingerprint

Gonadotropins
Steroids
Staining and Labeling
Testis
Basement Membrane
Testosterone
Fetus
Hypothalamic Hormones
Messenger RNA
Seminiferous Tubules
Pituitary Hormones
Antibodies
Sertoli Cells
Cytosol
Down-Regulation
Immunohistochemistry
Proteins

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Kuroda, T., Lee, M. M., Ragin, R. C., Hirobe, S., & Donahoe, P. K. (1991). Müllerian inhibiting substance production and cleavage is modulated by gonadotropins and steroids. Endocrinology, 129(6), 2985-2992.

Müllerian inhibiting substance production and cleavage is modulated by gonadotropins and steroids. / Kuroda, Tatsuo; Lee, Mary M.; Ragin, Richard C.; Hirobe, Seiichi; Donahoe, Patricia K.

In: Endocrinology, Vol. 129, No. 6, 12.1991, p. 2985-2992.

Research output: Contribution to journalArticle

Kuroda, T, Lee, MM, Ragin, RC, Hirobe, S & Donahoe, PK 1991, 'Müllerian inhibiting substance production and cleavage is modulated by gonadotropins and steroids', Endocrinology, vol. 129, no. 6, pp. 2985-2992.
Kuroda, Tatsuo ; Lee, Mary M. ; Ragin, Richard C. ; Hirobe, Seiichi ; Donahoe, Patricia K. / Müllerian inhibiting substance production and cleavage is modulated by gonadotropins and steroids. In: Endocrinology. 1991 ; Vol. 129, No. 6. pp. 2985-2992.
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