Follicle-stimulating hormone synthesis and fertility are intact in mice lacking SMAD3 DNA binding activity and SMAD2 in gonadotrope cells

Jérôme Fortin, Ulrich Boehm, Michael B. Weinstein, Jonathan M. Graff, Daniel J. Bernard

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The activin/inhibin system regulates follicle- stimulating hormone (FSH) synthesis and release by pituitary gonadotrope cells in mammals. In vitro cell line data suggest that activins stimulate FSH β-subunit (Fshb) transcription via complexes containing the receptor- regulated SMAD proteins SMAD2 and SMAD3. Here, we used a Cre-loxP approach to determine the necessity for SMAD2 and/or SMAD3 in FSH synthesis in vivo. Surprisingly, mice with conditional mutations in both Smad2 and Smad3 specifically in gonadotrope cells are fertile and produce FSH at quantitatively normal levels. Notably, however, we discovered that the recombined Smad3 allele produces a transcript that encodes the entirety of the SMAD3 C-terminal Mad homology 2 (MH2) domain. This protein behaves similarly to fulllength SMAD3 in Fshb transcriptional assays. As the truncated protein lacks the N-terminal Mad homology 1 (MH1) domain, these results show that SMAD3 DNAbinding activity as well as SMAD2 are dispensable for normal FSH synthesis in vivo. Furthermore, the observation that deletion of proximal exons does not remove all SMAD3 function may facilitate interpretation of divergent phenotypes previously described in different Smad3 knockout mouse lines.

Original languageEnglish (US)
Pages (from-to)1474-1485
Number of pages12
JournalFASEB Journal
Volume28
Issue number3
DOIs
StatePublished - 2014

Fingerprint

Follicle Stimulating Hormone
Fertility
DNA
Activins
Inhibins
Proteins
Mammals
Transcription
Knockout Mice
Exons
Assays
Alleles
Cells
Phenotype
Cell Line
Mutation

Keywords

  • Activin
  • Knockout
  • Pituitary
  • Reproduction

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology
  • Medicine(all)

Cite this

Follicle-stimulating hormone synthesis and fertility are intact in mice lacking SMAD3 DNA binding activity and SMAD2 in gonadotrope cells. / Fortin, Jérôme; Boehm, Ulrich; Weinstein, Michael B.; Graff, Jonathan M.; Bernard, Daniel J.

In: FASEB Journal, Vol. 28, No. 3, 2014, p. 1474-1485.

Research output: Contribution to journalArticle

Fortin, Jérôme ; Boehm, Ulrich ; Weinstein, Michael B. ; Graff, Jonathan M. ; Bernard, Daniel J. / Follicle-stimulating hormone synthesis and fertility are intact in mice lacking SMAD3 DNA binding activity and SMAD2 in gonadotrope cells. In: FASEB Journal. 2014 ; Vol. 28, No. 3. pp. 1474-1485.
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