Identification of a retinoic acid response element in the human oxytocin promoter.

Richard S, Zingg HH

The Journal of biological chemistry1 Nov 1991Cited by 52 (Europe PMC)

PMID1657967DOI10.1016/s0021-9258(18)54656-1PepBankPUB-01657967

Publisher page PubMedAsk about this study

Summary

Retinoids are known to have profound effects on cellular differentiation and embryo pattern formation. In the adult organism, retinoid acid (RA) receptors are present in a large variety of tissues, including brain. However, little is known of the precise roles of RA at these different sites. In the present study we have identified a novel potential target of RA action by identifying an RA response element (RARE) in the human oxytocin (OT) gene promoter. We have used DNA-mediated gene transfer techniques to introduce various portions of the OT 5'-flanking sequences next to the chloramphenicol acetyltransferase (CAT) gene in neuroblastoma cells. RA elicited a marked stimulation of the transcriptional activity of the OT promoter in cells cotransfected with either the human RA receptor alpha, beta, or gamma. In cells cotransfected with the RA receptor alpha, the ED50 of this response was 5 x 10(-10) M. The RA response could also be conferred to a heterologous promoter independent of orientation. 5'-Deletions as well as site-directed mutations demonstrated that four TGACC motifs, located at -162, -156, -103, and -83 in the OT promoter, are necessary for optimal RA induction. Mutation or deletion of any of these elements reduces significantly the RA response. Interestingly, the first two TGACC motifs overlap with the estrogen response element that we have previously characterized in this gene. Furthermore, the TGACC motif located at -83 overlaps with the CCAAT box. We further demonstrate that in neuroblastoma cells transfected with an RAR alpha expression vector expression of the endogenous OT gene is stimulated greater than 4-fold in response to RA. Our studies constitute the first report of a RARE in a neuropeptide gene and define a mechanism by which OT gene expression can be modulated by retinoic acid.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

No result from this study comes from a test of the peptide.

Natural levels measured1

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

01LabEndogenous levelIn vitro (cells)Mechanism
In neuroblastoma cells transfected with an RAR alpha expression vector, retinoic acid increased expression of the endogenous OT gene more than 4-fold.
In plain wordsIn cells, retinoic acid raised the cells' own oxytocin gene expression by more than 4 times.
Peptide
Oxytocin
Outcome
IncreaseEndogenous OT gene expression with retinoic acid
Study
n: not reported in source
Neuroblastoma cells transfected with OT promoter-CAT constructs
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Measurements
Endogenous OT gene expression fold increase
> 4 fold
RAR alpha-transfected neuroblastoma cells
Source sentences
Summary
We further demonstrate that in neuroblastoma cells transfected with an RAR alpha expression vector expression of the endogenous OT gene is stimulated greater than 4-fold in response to RA.
1 context sentence(design, population, supporting numbers)
Summary · context
We have used DNA-mediated gene transfer techniques to introduce various portions of the OT 5'-flanking sequences next to the chloramphenicol acetyltransferase (CAT) gene in neuroblastoma cells.
This result measures the body's own Oxytocin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-0165796705

Studies that did not test the peptide alone4

In this study, Oxytocin was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Oxytocin.

02LabNot a test of Oxytocin aloneIn vitro (cells)Mechanism
In neuroblastoma cells cotransfected with human RA receptor alpha, beta or gamma, retinoic acid markedly stimulated transcriptional activity of the human oxytocin promoter.
In plain wordsIn cells, retinoic acid strongly switched on the activity of the human oxytocin gene promoter.
Peptide
Oxytocin
Outcome
IncreaseOT promoter transcriptional activity with retinoic acid
Study
n: not reported in source
Neuroblastoma cells transfected with OT promoter-CAT constructs
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
RA elicited a marked stimulation of the transcriptional activity of the OT promoter in cells cotransfected with either the human RA receptor alpha, beta, or gamma.
1 context sentence(design, population, supporting numbers)
Summary · context
We have used DNA-mediated gene transfer techniques to introduce various portions of the OT 5'-flanking sequences next to the chloramphenicol acetyltransferase (CAT) gene in neuroblastoma cells.
In this study, Oxytocin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Oxytocin.
Show in the study text Report a problemFND-0165796701
03LabNot a test of Oxytocin aloneIn vitro (cells)Mechanism
In cells cotransfected with RA receptor alpha, the ED50 of the retinoic acid response of the oxytocin promoter was 5 x 10(-10) M.
In plain wordsIn cells, a very low retinoic acid concentration was enough to half-maximally switch on the oxytocin gene promoter.
Peptide
Oxytocin
Outcome
Not applicableED50 of retinoic acid response of the OT promoter
Study
n: not reported in source
Neuroblastoma cells transfected with OT promoter-CAT constructs
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
In cells cotransfected with the RA receptor alpha, the ED50 of this response was 5 x 10(-10) M.
1 context sentence(design, population, supporting numbers)
Summary · context
We have used DNA-mediated gene transfer techniques to introduce various portions of the OT 5'-flanking sequences next to the chloramphenicol acetyltransferase (CAT) gene in neuroblastoma cells.
In this study, Oxytocin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Oxytocin.
Show in the study text Report a problemFND-0165796702
04LabNot a test of Oxytocin aloneIn vitro (cells)Mechanism
The retinoic acid response could also be conferred to a heterologous promoter independent of orientation.
In plain wordsIn cells, the retinoic acid response could be moved to another promoter, in either direction.
Peptide
Oxytocin
Outcome
Not applicableRetinoic acid response transfer to a heterologous promoter
Study
n: not reported in source
Neuroblastoma cells transfected with OT promoter-CAT constructs
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
The RA response could also be conferred to a heterologous promoter independent of orientation.
1 context sentence(design, population, supporting numbers)
Summary · context
We have used DNA-mediated gene transfer techniques to introduce various portions of the OT 5'-flanking sequences next to the chloramphenicol acetyltransferase (CAT) gene in neuroblastoma cells.
In this study, Oxytocin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Oxytocin.
Show in the study text Report a problemFND-0165796703
05LabNot a test of Oxytocin aloneIn vitro (cells)Mechanism
In the OT promoter, four TGACC motifs were necessary for optimal retinoic acid induction; mutation or deletion of any of them significantly reduced the response.
In plain wordsIn cells, removing or changing any of four DNA motifs in the oxytocin promoter weakened its response to retinoic acid.
Peptide
Oxytocin
Outcome
DecreaseTGACC motifs required for RA induction of the OT promoter
Study
n: not reported in source
Neuroblastoma cells transfected with OT promoter-CAT constructs
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
5'-Deletions as well as site-directed mutations demonstrated that four TGACC motifs, located at -162, -156, -103, and -83 in the OT promoter, are necessary for optimal RA induction. Mutation or deletion of any of these elements reduces significantly the RA response.
1 context sentence(design, population, supporting numbers)
Summary · context
We have used DNA-mediated gene transfer techniques to introduce various portions of the OT 5'-flanking sequences next to the chloramphenicol acetyltransferase (CAT) gene in neuroblastoma cells.
In this study, Oxytocin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Oxytocin.
Show in the study text Report a problemFND-0165796704

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
11 Oct 2026, 20:03 UTC
Study results updated
Version 1
9 Oct 2026, 02:53 UTC
First added · source update from Europe PMC

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