Luteinizing Hormone Deficiency and Female Infertility in Mice Lacking the Transcription Factor NGFI-A (Egr-1)

TLDR

NGFI‑A is an immediate‑early transcription factor that links extracellular signals to gene expression, but no factor has been identified that specifically regulates luteinizing hormone synthesis. NGFI‑A activates LH‑β transcription by binding a conserved promoter site and acting synergistically with steroidogenic factor‑1. NGFI‑A‑deficient mice are infertile due to LH‑β deficiency, as evidenced by reduced LH‑β mRNA and pituitary‑specific defects revealed by ovariectomy.

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-β deficiency. Ovariectomy led to increased amounts of FSH-β but not LH-β messenger RNA, which suggested a pituitary defect. A conserved, canonical NGFI-A site in the LH-β 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-β transcription.