Molecular regulation of the oxytocin receptor in peripheral organs

Abstract

The oxytocin receptor belongs to the G-protein-coupled seven transmembrane receptor superfamily. Its main physiological role is regulating the contraction of uterine smooth muscle at parturition and the ejection of milk from the lactating breast. Oxytocin receptor expression is observed not only in the myometrium and mammary gland but also in the endometrium, decidua, ovary, testis, epididymis, vas deferens, thymus, heart and kidney, as well as in the brain. The expression profile shows a tissue-specific as well as a stage-specific pattern. The oxytocin receptor gene is a single-copy gene consisting of four exons and three introns, localized at 3p25-3p26·2 in the human chromosome. In transfection studies using a fusion construct containing the promoter region of the oxytocin receptor gene inserted in a reporter plasmid, neither proinflammatory cytokines nor oestrogen directly activate the gene. The nuclear fractions from up-regulated (term myometrium) and down-regulated (non-pregnant myometrium) tissues show differential patterns of protein binding to the 5′-flanking region, and a human homologue of chicken MafF has been cloned as a term-myometrium-specific oxytocin receptor modulator. The oxytocin receptor gene appears to be highly methylated. Methylation around intron 1 and in intron 3 might contribute to tissue-specific suppression of the gene. The oxytocin receptor is also regulated by desensitization, whose mechanism appears to involve loss of ligand-binding activity of the protein as well as suppression of the oxytocin receptor mRNA transcription. These findings taken together indicate that the oxytocin receptor is regulated in a very complicated manner, and the transcriptional regulatory elements critical for this regulation should be investigated further.

Maternal adversities during pregnancy and cord blood oxytocin receptor (OXTR) DNA methylation

“…However, further candidate genes should be investigated to improve our understanding of how the maternal psychosocial environment could shape the offspring's epigenome. One candidate gene is the oxytocin receptor gene (OXTR), which is expressed in several brain regions implicated in social behavior and bonding, as well as in various peripheral tissues (Kimura et al, 2003). The oxytocinergic system is implicated in reproductive behavior, such as induction of labor and lactation, and has important function in mother-child bonding and maternal psychological wellbeing, including depression and anxiety (Lonstein et al, 2014).…”

Beyond Labor: The Role of Natural and Synthetic Oxytocin in the Transition to Motherhood (2014/023)

“…In turn, the OTR is less available to bind with oxytocin potentially resulting in diminished biological and behavioral outcomes. 20 There are sensitive periods during mammalian development in which the environment can shape DNA methylation. 22 For instance, rodent models show that early maternal care can be linked to patterns of methylation in both maternal and offspring phenotypes with a transgenerational effect.…”

Siçanlarda yanikla indüklenen anksiyete artisina ve agri algisina santral ve periferik uygulanan oksitosinin etkisi

“…OT reseptörleri, miyometrium, meme bezi, endometriyum, desidua, over, testis, epididim, vas deferens, timus, kalp, böbrek ve beynin çe itli bölgelerinde bulunur (6). Yap s vazopressine benzeyen OT, adrenokortikotrofik hormon (ACTH) salg s n artt rmak yoluyla zay f bir antidiüretik etki de gösterir (7).…”

“…OT beyindeki etkisi ile sosyal ve seksüel davran lar n olu umunda da önemlidir (2,3). Do umda uterus düz kas kontraksiyonunu ve do um sonras emzirme esnas nda memeden süt ç k n düzenleyici rolünün (3,6) yan s ra, kardiyovasküler ve natriüretik düzenlemede rol ald da gösterilmi tir (8). OT dü ük dozlarda uyguland nda kendine özgü reseptörleri aktive ederek vazodilatasyon sa larken, yüksek dozlarda anjiyotensin-vazopressin (AVP) reseptörlerinin uyar lmas yla vazokonstriksiyona ba l hipertansiyona neden olur (8)…”