In vitro effect of oestradiol on thymidine uptake in pulmonary vascular smooth muscle cell: role of the endothelium

Abstract

1 The effect of different concentrations of oestradiol-171P (3-300 nM) on [3H]-thymidine uptake was studied in segments from canine pulmonary artery, and cultures of rat pulmonary vascular smooth muscle cells (VSMC).2 Incubation with oestradiol-1 7P for 24 h, potentiated in a concentration-dependent manner [3H]-thymidine uptake in VSMC cultures. 3 Oestradiol-1 71B potentiated thymidine uptake by pulmonary arterial segments but only when the endothelium had been removed. Autoradiography showed dense incorporation of radioactive thymidine in the vascular smooth muscle cells of the media. 4 The non-steroidal oestrogen, stilboestrol (300 nM), also significantly potentiated [3H]-thymidine uptake, in both VSMC cultures and pulmonary artery segments. Testosterone was ineffective at a similar concentration.5 Pre-incubation of the pulmonary VSMC with the anti-oestrogen tamoxifen (I ylM) antagonized the potentiating effect of oestradiol-171P on [3H]-thymidine incorporation. The effect of tamoxifen was less pronounced in pulmonary arterial segments. 6 These data suggest that oestrogen may promote proliferation of pulmonary VSMC. Endothelial injury or dysfunction may be an important factor in the expression of the oestrogenic effect. 7 We speculate that plasma oestrogen may be a contributing factor to the proliferative lesion observed in certain forms of pulmonary vascular injury in women.

Estrogen inhibits the vascular injury response in estrogen receptor β-deficient female mice

“…2, 17, and 18). The direct effects of E2 on the vasculature include rapid effects on vasomotor tone (19)(20)(21)(22), and longer-term effects on atherosclerosis (3,4,17,18,(23)(24)(25)(26) and vascular cell proliferation and migration (17,18,(27)(28)(29)(30)(31)(32). The longer-term effects of estrogens result from alterations in gene expression, and are believed to be mediated by estrogen receptors, which are ligand-activated transcription factors (33,34).…”

Human vascular smooth muscle cells express an estrogen receptor isoform

“…However, systemic effects of estrogens do not account fo ~" the majority of the observed atheroprotective effects of E2 [2.3,15,16]. In an effort to reveal additional pathways that may mediate the atheroprotective effects of E2, direct effects of E2 ol ~, vascular cells are currently being investigated (reviewed in [1 '] Direct effects of E2 on vascular cell function were first suggested decades ago [7,18] and have since been shown both in whole animal and in vitro studies [10,[19][20][21][22][23][24][25][26][27][28][29][30]. However, the signaling pathways involved in the direct effects of E2 on vascular cells are not yet characterized.…”

Regulation of Allergic Lung Inflammation in Rats: Interaction between Estradiol and Corticosterone

“…In addition, it has been demonstrated in vitro that estradiol increases the number of ß 2 -adrenoceptors in lung tissue, which indicates a regulatory role for this hormone on inflammatory lung responses [10]. Besides, estradiol promotes proliferation of pulmonary vascular smooth muscle cells and its effects may be accounted for by the development of the proliferative lesions in some forms of pulmonary vascular injury in women [8].…”

“…It can alter endothelial cell metabolism, thus suggesting an involvement with the inflammatory response [8,9]. In addition, it has been demonstrated in vitro that estradiol increases the number of ß 2 -adrenoceptors in lung tissue, which indicates a regulatory role for this hormone on inflammatory lung responses [10].…”