scholarly journals Estrogen Regulates Transcription of the Ovine Oxytocin Receptor Gene through GC-Rich SP1 Promoter Elements

Endocrinology ◽  
2006 ◽  
Vol 147 (2) ◽  
pp. 899-911 ◽  
Author(s):  
JoAnn G. W. Fleming ◽  
Thomas E. Spencer ◽  
Stephen H. Safe ◽  
Fuller W. Bazer

Establishment of pregnancy in ruminants results from paracrine signaling by interferon τ (IFNT) from the conceptus to uterine endometrial luminal epithelia (LE) that prevents release of luteolytic prostaglandin F2α 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 α (ESR1) and then oxytocin receptor (OXTR) gene expression followed by oxytocin-induced prostaglandin F2α 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 activator protein 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, E2, 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, progesterone receptor 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.

2016 ◽  
Vol 177 (1-3) ◽  
pp. 59-66 ◽  
Author(s):  
Stefanie Uhrig ◽  
Natalie Hirth ◽  
Laura Broccoli ◽  
Martina von Wilmsdorff ◽  
Manfred Bauer ◽  
...  

2015 ◽  
Vol 3 (1) ◽  
pp. e979681 ◽  
Author(s):  
E Nicole Dover ◽  
David E Mankin ◽  
Howard C Cromwell ◽  
Vipaporn Phuntumart ◽  
Lee A Meserve

2020 ◽  
Author(s):  
KUMARI ANUKRITI ◽  
KIRAN GULERIA ◽  
VIPIN TYAGI ◽  
AMITA SUNEJA ◽  
BASU DEV BANERJEE

BACKGROUND: The oxytocin (OXT)-oxytocin receptor (OXTR) system provides promising candidate gene for studies of genetic contributions to prematurity. OBJECTIVE: Quantification and comparison of oxytocin receptor (OXTR) gene expression and serum OXT levels in the blood and amnion of women delivering preterm and evaluation of the correlation between OXTR gene expression in blood and amnion with serum OXT levels in them. METHODS: 70 pregnant women in spontaneous labor delivering vaginally preterm i.e < 37 weeks and equal number of matched controls delivering spontaneously at term (37-42 weeks) were recruited. Maternal serum OXT levels taken in active stage of labor (i.e 4 cm cervical dilatation) were quantified by ELISA. Gene expression studies in the maternal blood and amnion were done by using real time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The mean serum OXT level in PTL was 48.56 +- 6.97 pg/ml; significantly higher than in controls (43.00 +- 3.96 pg/ml), p<0.001. OXTR gene expression both in maternal blood (2.5 times) and amnion (3.5 times) were significantly higher in PTL. A significant positive correlation was observed between serum OXT levels and OXTR gene expression in amnion (r = -0.190, p = 0.025). CONCLUSIONS: The serum OXT levels and OXTR gene expression in amnion surge significantly in active phase of PTL. Thus, amnion probably links OXT-PTGs autocrine paracrine circuit to facilitate PTL. Future studies are needed to devise better OXTR receptor antagonists preferably acting on amnionic OXTRs to prevent PTL. KEYWORDS: Preterm birth, Preterm labor, Oxytocin, Oxytocin receptor, Placenta, Amnion


2008 ◽  
Vol 60 (3) ◽  
pp. 379-387 ◽  
Author(s):  
Natasa Kovacevic-Grujicic ◽  
Kazunari Yokoyama ◽  
Milena Stevanovic

In this study, we examine the role of three highly conserved putative binding sites for Myc-associated zinc finger protein (MAZ) in regulation of the human SOX3 gene expression. Electrophoretic mobility shift and supershift assays indicate that complexes formed at two out of three MAZ sites of the human SOX3 promoter involve ubiquitously expressed MAZ protein. Furthermore, in cotransfection experiments we demonstrate that MAZ acts as a positive regulator of SOX3 gene transcription in both undifferentiated and RA-differentiated NT2/D1 cells. Although MAZ increased both basal and RA-induced promoter activity, our results suggest that MAZ does not contribute to RA inducibility of the SOX3 promoter during neuronal differentiation of NT2/D1 cells.


1994 ◽  
Vol 344 (1309) ◽  
pp. 291-304 ◽  

The oxytocin receptor, a seven transmembrane domain, G protein-linked receptor molecule, plays a central role in determining the endocrine function of the ruminant uterine endometrium. During non- pregnant cycles the control of this molecule by circulating steroid hormones leads to regression of the corpora lutea. The kinetics of the mechanisms involved determine the time at which luteolysis occurs, and therefore the length of the oestrous cycle. In pregnancy, secretions of the trophoblast block endometrial oxytocin receptor gene expression and lead to luteal maintenance. An understanding of the molecular mechanisms involved in the steroidal control of oxytocin receptor gene expression will provide an explanation for the relative constancy of oestrous cycle lengths in non-pregnant animals. Unravelling the way in which trophoblast products block expression of the oxytocin receptor gene will lead to a better understanding of the reasons for the high rate of embryonic loss in domestic ruminants.


1995 ◽  
Vol 53 (3) ◽  
pp. 553-560 ◽  
Author(s):  
Richard Ivell ◽  
Werner Rust ◽  
Almuth Einspanier ◽  
Stefan Hartung ◽  
Michael Fields ◽  
...  

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