The immediate-early transcription factor NGFl-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 NGFl-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 NGFl-A site in the LH-beta promoter was required for synergistic activation by NGFl-A and steroidogenic factor-1 (SF-1). NGFl-A apparently influences female reproductive capacity through its regulation of LH-beta transcription.