Progesterone inhibition of oxytocin signaling in endometrium

Abstract

Expression of the oxytocin receptor (OXTR) in the endometrium of ruminant species is regulated by the ovarian steroids progesterone (P) and estradiol (E). Near the end of the estrous cycle, long-term exposure of endometrial epithelial cells to P results in loss of genomic P receptors (PGRs), leading to an increase in E receptors (ERs). Genomic regulation of the OXTR is mediated via suppression of ER signaling by P. Upon OT binding at the plasma membrane of endometrial cells, a signaling cascade is generated stimulating release of prostaglandin F2α (PGF2α). Transport of PGF2α to the ovary results in release of OT by luteal cells in a positive feedback loop leading to luteal regression. This signaling cascade can be rapidly blocked by exposing endometrial cells to physiologic levels of P. This mini review will focus on the mechanisms by which P may act to block OXTR signaling and the luteolytic cascade in the ruminant endometrium, with special focus on both non-genomic signaling pathways and non-receptor actions of P at the level of the plasma membrane. While this review focuses on ruminant species, non-classical blockage of OXTR signaling may be important for fertility in women.

Spatio-specific regulation of endocrine-responsive gene transcription by periovulatory endocrine profiles in the bovine reproductive tract

“…Similarly, the expression of OXTR is known to be downregulated during dioestrus; its transcript abundance is maximal around oestrus and decreases progressively during early to mid-dioestrus (Wijayagunawardane et al 1998;. The downregulation of OXTR expression may be triggered by increased P4 levels via non-genomic actions (Bishop 2013). Interestingly, we observed a higher ESR2 expression in cows with greater circulating P4 at Day 7, which contrasts with the previous report of Okumu et al (2010), who documented an inhibiting effect of P4 on ESR2 gene expression at mid-dioestrus.…”

“…Gene expression of PGR, ESR2 and OXTR are upregulated by E2 and downregulated by P4 (Okumu et al 2010;Bishop 2013). SLC2A1, AKR1C4, LPL and SERPINA14 are genes related to histotroph composition and conceptus maintenance (Ulbrich et al 2009a(Ulbrich et al , 2009bForde et al 2010).…”

Cloprostenol administration in the first week postpartum reduces expression of oxytocin receptors in the endometrium in Holstein-Zebu cows

“…Moreover, the increase of OXTR gene expression in endometrium from D7 to D14 postpartum is consistent with the hormonal profiling found in the cows. Progesterone has a suppressive role on expression of oxytocin receptor whereas estradiol has a stimulating effect (Vallet et al, 1990, Bishop et al, 2013, despite both being required for appropriated expression. In this present study, the concentration of serum progesterone was low during the 28 postpartum days, although it started increasing after D14, whereas the estradiol concentrations increased between D7 and D14 postpartum.…”

<b>Ação do 17&#946;-estradiol na síntese de PGF2&#945; endometrial em vacas</b>

“…Relatou-se em estudos que o estradiol controla a expressão de OXTR e aumenta as concentrações de PGF2α no endométrio de ruminantes ASSELIN et al, 1996;VALLET;BATTEN, 1990;FLEMING et al, 2006). As mudanças nas concentrações de hormônios esteroides, estradiol e progesterona (P4), que ocorrem durante o ciclo estral, são fundamentais para coordenar a presença dos receptores endometriais de ocitocina (OXTR), estradiol (ESR) e progesterona (PGR) OKUMU et al, 2010;BISHOP, 2013). Elevadas concentrações de PGR no diestro inicial inibem a expressão de ESR, e consequentemente, de OXTR no endométrio.…”