Desensitization of beta2-adrenoceptor function in non-pregnant rat myometrium is modulated by sex steroids

Abstract

The effects of in vivo treatment with estrogen and progesterone on isoproterenol-induced uterine relaxation and 2 -adrenoceptor ( 2 AR) mRNA production in nonpregnant rat myometrium were investigated. Whether homologous myometrial desensitization of 2 AR function was dependent on or modulated by the two steroids was also examined.Estrogen treatment alone or in combination with progesterone reduced maximal relaxation (E max ) of isolated uterine strips subsequently challenged with isoproterenol whereas progesterone alone had no effect on this parameter. The reduction was accompanied by an enhanced 2 AR mRNA concentration. The concentration of isoproterenol giving half-maximal relaxing response (EC 50 ) increased following estrogen treatment and this effect was curbed by progesterone.Isoproterenol had no effect on 2 AR transcription irrespective of the steroid regimes employed. E max of isolated uterine strips was reduced following prolonged in vivo treatment with isoproterenol but the effect was found only when estrogen alone was administered concomitantly. Finally, in vivo treatment with isoproterenol increased EC 50 of uterine strips subsequently stimulated with isoproterenol in vitro. This effect was independent of steroid treatment.We conclude that homologous desensitization of 2 AR function in non-pregnant rat myometrium in terms of sensitivity (EC 50 ) is independent of sex steroids but in terms of maximal response (E max ) occurs only in the presence of estrogen. We speculate whether progesterone withdrawal in connection with the well-known estrogen dominance at rat parturition may strengthen the desensitization induced by 2 AR activation and thus contribute to the transformation of the uterus from a quiescent to a highly contractile organ.

In vitro relaxant and spasmolytic effects of constituents from Viburnum prunifolium and HPLC quantification of the bioactive isolated iridoids

“…These effects could be confirmed by a characteristic loss of tracheal tone (for about 30 min) to continued occupancy of ␤ 2 -adrenoceptors due to subsequent agonist stimulation (Katsunuma et al, 2000). The ␤-adrenergic desensitization has also been observed in vitro rat myometrium (Johansson and Andersson, 1981;Engstrom et al, 2001). In conclusion, based on our results, we suggest that Viburnum prunifolium is able to relax isolated rabbit jejunum and guinea-pig trachea through an interaction with the ␤-adrenergic system.…”

Pregnancy-induced decrease in the relaxant effect of terbutaline in the late-pregnant rat myometrium: role of G-protein activation and progesterone

“…This effect of estrogen was not altered by concomitant progesterone treatment. It was concluded that the process of b 2 -AR function desensitization was independent of the sex steroids (Engstrom et al 2001). Our experiment revealed increased levels of b 2 -AR mRNA and b 2 -AR on days 20 and 22, respectively.…”

“…Earlier studies suggested that the presence or absence of progesterone can alter the effect of b 2 -AR agonists on the pregnant myometrium (Dowell et al 1994, Engstrom et al 2001. On the basis of the sex hormone levels at the end of pregnancy, the pregnant animals were treated with progesterone for 7 days.…”

Estrogen Reduces Cardiac Injury and Expression of β1-Adrenoceptor upon Ischemic Insult in the Rat Heart

“…Estrogen has been shown to suppress the responsiveness to ␤-AR stimulation in the hypothalamus of rats (Ungar et al, 1993;Ansonoff and Etgen, 2001) and myometrium of rats (Ruzycky and DeLoia, 1997;Engstrom et al, 2001). In the hypothalamus, estrogen uncouples the receptor and the G protein (Ungar et al, 1993;Ansonoff and Etgen, 2001), whereas in the myometrium, estrogen increases the ␤-ARinactivating kinase (Ruzycky and DeLoia, 1997).…”