Steroidogenic Factor 1 Regulates Transcription of the Inhibin B Coreceptor in Pituitary Gonadotrope Cells

Yeu Farn Lin, Gauthier Schang, Evan R.S. Buddle, Hailey Schultz, Thea L. Willis, Frederique Ruf-Zamojski, Michel Zamojski, Natalia Mendelev, Ulrich Boehm, Stuart C. Sealfon, Cynthia L. Andoniadou, Daniel J. Bernard

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The inhibins control reproduction by suppressing follicle-stimulating hormone synthesis in pituitary gonadotrope cells. The newly discovered inhibin B coreceptor, TGFBR3L, is selectively and highly expressed in gonadotropes in both mice and humans. Here, we describe our initial characterization of mechanisms controlling cell-specific Tgfbr3l/TGFBR3L transcription. We identified two steroidogenic factor 1 (SF-1 or NR5A1) cis-elements in the proximal Tgfbr3l promoter in mice. SF-1 induction of murine Tgfbr3l promoter-reporter activity was inhibited by mutations in one or both sites in heterologous cells. In homologous cells, mutation of these cis-elements or depletion of endogenous SF-1 similarly decreased reporter activity. We observed nearly identical results when using a human TGFBR3L promoter-reporter. The Tgfbr3l gene was tightly compacted and Tgfbr3l mRNA expression was essentially absent in gonadotropes of SF-1 (Nr5a1) conditional knockout mice. During murine embryonic development, Tgfbr3l precedes Nr5a1 expression, though the two transcripts are fully colocalized by embryonic day 18.5 and thereafter. Collectively, these data indicate that SF-1 directly regulates Tgfbr3l/TGFBR3L transcription and is required for postnatal expression of the gene in gonadotropes.

Original languageEnglish
Article numberbqac131
JournalEndocrinology
Volume163
Issue number11
DOIs
StatePublished - 1 Nov 2022

Keywords

  • cell line
  • inhibin
  • knockout mouse
  • pituitary
  • receptor
  • transcription

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