Effects of exogenous female sex-steroid hormones on lymphocyte beta(2)-adrenoceptors in normal females

We have previously shown that lymphocyte beta(2)-adrenoceptors (AR) are under cyclical control of sex-steroid hormones with greater receptor density during the luteal phase of the menstrual cycle. It has also been postulated that abnormal cyclical regulation of beta(2)-AR might be a possible mechanism for premenstrual asthma. The effects of exogenous female sex-steroid hormones on lymphocyte beta(2)-AR function were studied in eight normal healthy females. They were evaluated at two successive menstrual cycles, during the follicular phase (day 1-6). They were randomized to receive single oral doses of either ethinyloestradiol 50 mu g or medroxyprogesterone 10 mg in a cross-over study. Lymphocyte beta(2)-AR parameters were evaluated at baseline (t(0)), 24 h (t(24)) and 72 h (t(72)) after ingestion. Baseline levels of progesterone and oestradiol were comparable on both cycles. Receptor density (beta(max)) increased significantly (P<0.01) from t(0) after progesterone but not oestradiol at t(24): a 1.39-fold geometric mean difference (95% CI 0.96-2.00) between t(24) vs t(0). Receptor affinity (K-d) and maximal cAMP response to isoprenaline (E(max)) were not altered by either treatment. These results show that exogenous progesterone but not oestradiol, given during the follicular phase, significantly increased beta(2)-AR. This, therefore, suggests that endogenous progesterone is probably responsible for previously observed increase in B-max during the luteal phase of the female menstrual cycle. These findings may suggest possible therapeutic strategies for modulation of beta(2)-AR in premenstrual asthma.