Cyclical expression of egr-1/NGFI-A in the rat anterior pituitary: a molecular signal for ovulation?
Molecular genetic studies of egr-1/NGFI-A have recently established a key role for this immediate early gene in anterior pituitary development, and particularly in transcriptional regulation of the LH beta-subunit gene. These studies, using null mutant mice, addressed the developmental aspects of gonadotrophin gene regulation by egr-1 and, because of the limitations of this approach, did not address the role of egr-1 in adult reproductive physiology. Using the rat, we have now investigated the expression of egr-1 during the female reproductive cycle, and have found evidence of cyclical changes in anterior pituitary egr-1 expression, at mRNA, protein, and DNA binding activity levels. Specifically, we have shown that egr-1 mRNA is significantly elevated during proestrous, and conversely suppressed on the subsequent day of oestrous. We have also demonstrated significantly raised levels of an approximately 70 kDa Egr-1 immunoreactive protein band during the night of proestrous, together with markedly raised levels of a Egr-1 consensus sequence DNA binding complex. These studies are indicative of both direct egr-1 gene regulation by oestrogen, and also regulation by GnRH. Finally, we have sequenced previously uncharacterized regions of the egr-1 gene and found evidence of a potential oestrogen response element. Our findings are consistent with the hypothesis that Egr-1 forms at least part of the molecular signal for ovulation in the pituitary.
Slade
J P
JP
School of Biosciences, Cardiff University, Cardiff, UK.
Carter
D A
DA
D000818:Animals; D016384:Consensus Sequence / Q000235:genetics; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051766:Early Growth Response Protein 1; D004971:Estrus / Q000502:physiology*; D005260:Female; D017874:Immediate-Early Proteins; D007158:Immunologic Techniques; D010060:Ovulation / Q000502:physiology*; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011359:Proestrus / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D004247:DNA