Loss of the protein NUPR1 (p8) leads to delayed LHB expression, delayed ovarian maturation, and testicular development of a Sertoli-cell-only syndrome-like phenotype in mice

Christina M. Million Passe, Crystal R. White, Michael W. King, Phillip L. Quirk, Juan L. Iovanna, Christine C. Quirk

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

The high mobility group factor NUPR1, also known as p8 and com1, plays a role in temporal expression of the beta subunit of luteinizing hormone, LHB, during gonadotroph development. At Embryonic Day (e) 16.5, LHB is detectable in wild-type (Nupr1+/+) but not Nupr1 knockout (Nupr1-/-) mice. LHB is initiated by e17.5 in Nupr1-/- mice, and expression is fully recovered by Postnatal Day (p) 2. Factors indicative of pituitary maturation, GATA2, CGA, and TSH, are not differentially expressed in Nupr1 -/- and Nupr1+/+ embryos at e17.5. Therefore, the delay in LHB expression does not appear to result from delayed pituitary development. In addition, the role of NUPR1 in gonadotropin expression appears specific for LHB, as no difference in FSHB is observed in Nupr1-/- and Nupr1 +/+ embryos. The gonads are also impacted by the absence of NUPR1. Ovaries of female Nupr1-/- mice lack corpora lutea (CL) at 8 wk, an age at which CL are present in all Nupr1+/+ littermates. Sexual maturity is recovered by 11 wk in Nupr1-/- mice. Conversely, the testes of Nupr1-/- males appear normal through 8 mo of age. By 10 mo, however, these mice develop a condition in which a significant number of seminiferous tubules lack germ cells, an abnormality reminiscent of human Sertoli-cell-only syndrome. NUPR1 is undetectable in Nupr1+/+ gonadotrophs by p2 and remains absent in adulthood, but quantitative PCR analysis indicates Nupr1+/+ adult ovaries and testes express Nupr1 mRNA. Therefore, the ovarian and testicular phenotypes may be due to the loss of NUPR1 directly at the gonads.

Original languageEnglish (US)
Pages (from-to)598-607
Number of pages10
JournalBiology of reproduction
Volume79
Issue number4
DOIs
StatePublished - Oct 1 2008

Keywords

  • Gonadotroph
  • Luteinizing hormone
  • NUPR1
  • Ovary
  • p8
  • Pituitary
  • Sertoli-cell-only syndrome
  • Testis

ASJC Scopus subject areas

  • Cell Biology

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