OXTR Membrane Protein Introduction

Introduction of OXTR

OXTR is an approximately 42.8 kDa G protein-coupled receptor (GPCR) and consists of 389 amino acids. In humans, this protein is encoded by the OXTR gene which is located on the chromosome 3p25.3. The OXTR gene codes for the oxytocin receptor and is a member of G-protein coupled seven-transmembrane receptor family. This receptor is found to be expressed on myoepithelial cells of the mammary gland, and also on endometrium and myometrium of the uterus at the end age of the pregnancy. The study showed that OXTR gene spans about 17 kb and contains 4 exons. Among them, exons 1 and 2 correspond to the 5-prime non-coding region, followed by exons 3 and 4 responsible for amino acids of the receptor. Furthermore, Southern blot analysis indicated that OXTR is present in single copy in the human genome.

Function of OXTR Membrane Protein

OXT is a peptide composed of oligopeptide chains of 9 amino acids. Its receptor, known as OXTR, spans 19.2 kb on chromosome 3 and is expressed in humans throughout the body in reproductive tissues and neural regions, including the amygdala, hypothalamus, frontal cortex, and olfactory nucleus. The OXT-OXTR system plays an essential role in several aspects of the reproductive system, functioning as an inducer of mammary gland proliferation, milk ejection and of uterine contractions during parturition, as well as the ejaculation in the male. It can also promote natriuresis and development of male aggression and offspring relationships. The activity of OXTR is mediated by G proteins that activate some different second messengers. It contains several dozen SNPs (single nucleotide polymorphism) that have been genotyped in association studies of varieties of neurophysiology and behaviors in humans. OXTR SNPs are correlated with emotional regulation, personality traits, prosociality ratings, empathy and social communication, reduced physiological reactivity to stress, and other social and biological traits.

Fig.1 Schematic representation of the CD38/OXT axis in neurohypophysis. (Malavasi, 2010)

Application of OXTR Membrane Protein in Literature

1. Wade M., et al. Birth weight interacts with a functional variant of the oxytocin receptor gene (OXTR) to predict executive functioning in children. Dev Psychopathol. 2018, 30(1), 203-211. PubMed ID: 28511728
   
   

   Genetic variation in the oxytocin receptor (OXTR) gene is related to several psychiatric conditions featured by deficits in executive functioning (EF). The findings suggested that OXTR is possibly associated with discrete neurocognitive abilities in the child, and these effects may be regulated by intrauterine conditions correlated with fetal growth and development.

2. Cleveland H.H., et al. Transactions Between Substance Use Intervention, the Oxytocin Receptor (OXTR) Gene, and Peer Substance Use Predicting Youth Alcohol Use. Prev Sci. 2018, 19(1), 15-26. PubMed ID: 28150062
   
   

   The report investigates that oxytocin receptor (OXTR) genes moderation of associations among exposure to a substance misuse intervention, average peer substance usage, and adolescents’ alcohol use during the ninth grade.

3. Beach S.R.H., et al. Prevention of early substance use mediates, and variation at SLC6A4 moderates, SAAF intervention effects on OXTR methylation. Prev Sci. 2018, 19(1), 90-100. PubMed ID: 27655391
   
   

   The results indicate that for susceptible youth, for instance, "s" allele carriers, preventive intervention is likely to "get under the skin" in a manner potentially valuable for long-term outcomes. Herein, this paper discusses implications for examination of OXTR methylation in future prevention studies.

4. Ebner N.C., et al. Associations between oxytocin receptor gene (OXTR) methylation, plasma oxytocin, and attachment across adulthood. Int J Psychophysiol. 2018. PubMed ID: 29410310
   
   

   OT exerts its functions through OT receptors, which are encoded by oxytocin receptor (OXTR) genes. Data contribute to growing evidence showing that the epigenetic modification of genes regulating OT pathways as well as endogenous OT expressions are related to the means that people establish and maintain intimate social relationships.

5. Veras A.B., et al. Rare missense coding variants in oxytocin receptor (OXTR) in schizophrenia cases are associated with early trauma exposure, cognition and emotional processing. J Psychiatr Res. 2018, 97, 58-64. PubMed ID: 29190530
   
   

   Cases with rare OXTR SNVs have less negative and affective symptoms than others, but similar psychotic symptoms and cognitive deficits. The clinical characteristics of these cases occur in correlation with exposure to early trauma, particularly sexual abuse, which may influence the expression of schizophrenia in subjects carrying specific SNVs in the OXTR.

OXTR Preparation Options

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Reference

1. Malavasi F, et al. (2010). The hidden life of NAD+-consuming ectoenzymes in the endocrine system. J Mol Endocrinol. 45(4), 183-191.

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