Luteinizing hormone deficiency and female infertility in mice lacking the transcription factor NGFI-A (Egr-1).
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.
Lee
S L
SL
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Sadovsky
Y
Y
Swirnoff
A H
AH
Polish
J A
JA
Goda
P
P
Gavrilina
G
G
Milbrandt
J
J
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D005260:Female; D005640:Follicle Stimulating Hormone / Q000235:genetics; D037201:Follicle Stimulating Hormone, beta Subunit; D051717:Fushi Tarazu Transcription Factors; D005786:Gene Expression Regulation; D018390:Gene Targeting; D006062:Gonadotropins / Q000494:pharmacology; D018398:Homeodomain Proteins; D017874:Immediate-Early Proteins; D007247:Infertility, Female / Q000235:genetics*; D007986:Luteinizing Hormone / Q000032:analysis / Q000172:deficiency* / Q000235:genetics*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010053:Ovary / Q000187:drug effects / Q000502:physiology; D010902:Pituitary Gland / Q000378:metabolism; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection; D014599:Uterus / Q000187:drug effects; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D037201:Follicle Stimulating Hormone, beta Subunit; D051717:Fushi Tarazu Transcription Factors; D006062:Gonadotropins; D018398:Homeodomain Proteins; D017874:Immediate-Early Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone