Naturally Occurring Genetic Variants in the Oxytocin Receptor Alter Receptor Signaling Profiles.

ABSTRACT: The hormone oxytocin is commonly administered during childbirth to initiate and strengthen uterine contractions and prevent postpartum hemorrhage. However, patients have wide variation in the oxytocin dose required for a clinical response. To begin to uncover the mechanisms underlying this variability, we screened the 11 most prevalent missense genetic variants in the oxytocin receptor (OXTR) gene. We found that five variants, V45L, P108A, L206V, V281M, and E339K, significantly altered oxytocin-induced Ca²⁺ signaling or β-arrestin recruitment and proceeded to assess the effects of these variants on OXTR trafficking to the cell membrane, desensitization, and internalization. The variants P108A and L206V increased OXTR localization to the cell membrane, whereas V281M and E3

SUBMITTER: Malik M 

PROVIDER: S-EPMC8506602 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature