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

SL Lee, Y Sadovsky, AH Swirnoff, JA Polish, P Goda… - Science, 1996 - science.org
SL Lee, Y Sadovsky, AH Swirnoff, JA Polish, P Goda, G Gavrilina, J Milbrandt
Science, 1996science.org
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 …
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.
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