Luteinizing hormone deficiency and female infertility in mice lacking the transcription factor NGFI-A (Egr-1)

Science. 1996 Aug 30;273(5279):1219-21. doi: 10.1126/science.273.5279.1219.

Abstract

The immediate-early transcription factor NGFI-A (also called Egr-1, zif/268, or Krox-24) is thought to couple extracellular signals to changes in gene expression. Although activins and inhibins regulate follicle-stimulating hormone (FSH) synthesis, no factor has been identified that exclusively regulates luteinizing hormone (LH) synthesis. An analysis of NGFI-A-deficient mice derived from embryonic stem cells demonstrated female infertility that was secondary to LH-beta deficiency. Ovariectomy led to increased amounts of FSH-beta but not LH-beta messenger RNA, which suggested a pituitary defect. A conserved, canonical NGFI-A site in the LH-beta promoter was required for synergistic activation by NGFI-A and steroidogenic factor-1 (SF-1). NGFI-A apparently influences female reproductive capacity through its regulation of LH-beta transcription.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • DNA-Binding Proteins / genetics*
  • Early Growth Response Protein 1
  • Female
  • Follicle Stimulating Hormone / genetics
  • Follicle Stimulating Hormone, beta Subunit
  • Fushi Tarazu Transcription Factors
  • Gene Expression Regulation*
  • Gene Targeting
  • Gonadotropins / pharmacology
  • Homeodomain Proteins
  • Immediate-Early Proteins*
  • Infertility, Female / genetics*
  • Luteinizing Hormone / analysis
  • Luteinizing Hormone / deficiency*
  • Luteinizing Hormone / genetics*
  • Male
  • Mice
  • Molecular Sequence Data
  • Ovary / drug effects
  • Ovary / physiology
  • Pituitary Gland / metabolism
  • Promoter Regions, Genetic
  • Receptors, Cytoplasmic and Nuclear
  • Steroidogenic Factor 1
  • Transcription Factors / genetics*
  • Transfection
  • Uterus / drug effects
  • Zinc Fingers

Substances

  • DNA-Binding Proteins
  • Early Growth Response Protein 1
  • Egr1 protein, mouse
  • Follicle Stimulating Hormone, beta Subunit
  • Fushi Tarazu Transcription Factors
  • Gonadotropins
  • Homeodomain Proteins
  • Immediate-Early Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Steroidogenic Factor 1
  • Transcription Factors
  • steroidogenic factor 1, mouse
  • Luteinizing Hormone
  • Follicle Stimulating Hormone