Reduced Expression of Immunoreactive β₂-Adrenergic Receptor Protein in Human Myometrium with Labor

Abstract

A considerable body of evidence exists suggesting that the beta(2)-adrenergic receptor (beta(2)-AR) mediates uterine relaxation. However, little information exists on the localization, distribution, or expression of beta(2)-ARs in the human myometrium during the nonpregnant to labor transition. We have used immunochemical methods to investigate beta(2)-AR localization and expression in the nonpregnant, term pregnant, and term parturient uterus. Myometrial biopsies were obtained from 1) nonpregnant, menstruating women undergoing hysterectomy; 2) singleton term pregnant women undergoing elective cesarean section before the onset of labor; or 3) singleton term pregnant women undergoing emergency cesarean section after spontaneous labor. Tissues were processed for immunohistochemistry, immunofluorescence, and Western blotting and a primary polyclonal antibody specific to the human beta(2)-AR to identify immunoreactive myometrial beta(2)-AR. Protein levels were subsequently quantified by densitometry relative to rat brain protein. Immunohistochemistry and immunofluorescence demonstrated the presence of beta(2)-AR predominantly at the plasma membrane and also in the cytosol of myometrial cells. A 2-fold decrease in protein levels of the beta(2)-AR was apparent in the myometrium of labor compared with that of nonpregnant and pregnant nonlaboring women (P < 0.05). These results demonstrate that down-regulation of beta(2)-AR protein with labor may constitute a contributory mechanism by which uterine quiescence is removed at term.

In Vitro and in Vivo Pharmacological Characterization of Ethyl-4-{trans-4-[((2S)-2-hydroxy-3-{4-hydroxy-3[(methylsulfonyl)amino]-phenoxy}propyl) Amino]cyclohexyl}benzoate Hydrochloride (SAR150640), a New Potent and Selective Human β3-Adrenoceptor Agonist for the Treatment of Preterm Labor

“…In addition, the myometrial ␤ 3 -adrenoceptor seems to be resistant to agonist-induced desensitization (Rouget et al, 2004). By contrast, ␤ 2 -adrenoceptor expression is either decreased (Breuiller et al, 1987;Chanrachakul et al, 2003) or unchanged (Gsell et al, 2000) at the end of pregnancy, and there is a loss of response to ␤ 2 -mimetics after chronic exposure to these drugs (Berg et al, 1983). This might partly explain the lack of efficacy of ␤ 2 -mimetics at the end of pregnancy.…”

Expression of scaffolding, signalling and contractile-filament proteins in human myometria: effects of pregnancy and labour

“…Thus, to simply maintain a constant proportion of a particular protein relative to total cellular protein content is, in itself, an important adaptation to the physiological stresses imposed on the uterus during pregnancy. This will also ensure the requisite presence of components of the contractile response if parturition occurs, at least in part, as a result of the release of inhibitory influences [23,24,[34][35][36]. The fact that no further changes in the proportions of ROK, MLC 20 , and caldesmon, nor of α-actin, caveolin-1 and caveolin-2, were observed with the onset of labour suggests that differential translational regulation of these molecules is not a necessity for the integrated uterine contractile response of parturition.…”

“…Several studies have assessed in human myometrium the transcriptional or translational changes occurring in expression of molecules that influence uterine quiescence [22][23][24]. In contrast, there is far less comparative information on the effect of pregnancy and labour on myometrial expression of proteins implicated in signalling pathways leading to direct contractile activation; that which is available for individual proteins is often contradictory [25,26].…”

Effects and Selectivity of CL 316243, Beta-3-Adrenoceptor Agonist, in Term-Pregnant Rat Myometrium

“…By contrast, β 2 -adrenoceptor expression is either decreased [13] or unchanged [14] at the end of pregnancy, and there is a loss of response to β 2 -mimetics after chronic exposure to these drugs [15]. This might partly explain the lack of efficacy of β 2 -mimetics at the end of pregnancy.…”