1: Endocrinology. 2005 Oct 27; [Epub ahead of print] 

Estrogen regulates transcription of the ovine oxytocin receptor gene through
GC-rich SP1 promoter elements.

Fleming JG, Spencer TE, Safe SH, Bazer FW.

Center for Animal Biotechnology and Genomics, Department of Animal Science, and
Department of Veterinary Physiology and Pharmacology, Texas A&M University,
College Station, Texas 77843 USA.

Establishment of pregnancy in ruminants results from paracrine signaling by
interferon tau(IFNT) from the conceptus to uterine endometrial luminal (LE)
epithelia that prevents release of luteolytic prostaglandin F2alpha (PGF)
pulses. In cyclic and pregnant ewes, progesterone down-regulates progesterone
receptor (PGR) gene expression in LE. In cyclic ewes, loss of PGR allows for
increases in estrogen receptor alpha(ESR1) and then oxytocin receptor (OXTR)
gene expression followed by oxytocin-induced PGF pulses. In pregnant ewes, IFNT
inhibits transcription of the ESR1 gene, which presumably inhibits OXTR gene
transcription. Alternatively, IFNT may directly inhibit OXTR gene transcription.
The 5' promoter/enhancer region of the ovine OXTR gene was cloned and found to
contain predicted binding sites for AP-1, SP1 and PGR, but not for ESR1.
Deletion analysis showed that the basal promoter activity was dependent on the
region from -144 to -4 bp that contained only SP1 sites. IFNT did not affect
activity of the OXTR promoter. In cells transfected with ESR1, estradiol-17beta
and ICI 182,780 increased promoter activity due to GC-rich SP1 binding sites at
positions -104 and -64. Mutation analyses showed that the proximal SP1 sites
mediated ESR1 action as well as basal activity of the promoter. In response to
progesterone, PGR-B also increased OXTR promoter activity. SP1 protein was
constitutively expressed and abundant in the LE of the ovine uterus. These
results support the hypothesis that the antiluteolytic effects of IFNT are
mediated by direct inhibition or silencing of ESR1 gene transcription, thereby
precluding ESR1/SP1 from stimulating OXTR gene transcription.

PMID: 16254027 [PubMed - as supplied by publisher]


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