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) ar e under cyclical control of sex-steroid hormones with greater receptor density during the luteal phase of the menstrual cycle. It has also b een postulated that abnormal cyclical regulation of beta(2)-AR might b e a possible mechanism for premenstrual asthma. The effects of exogeno us female sex-steroid hormones on lymphocyte beta(2)-AR function were studied in eight normal healthy females. They were evaluated at two su ccessive menstrual cycles, during the follicular phase (day 1-6). They were randomized to receive single oral doses of either ethinyloestrad iol 50 mu g or medroxyprogesterone 10 mg in a cross-over study. Lympho cyte 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 b ut 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 maxi mal cAMP response to isoprenaline (E(max)) were not altered by either treatment. These results show that exogenous progesterone but not oest radiol, given during the follicular phase, significantly increased bet a(2)-AR. This, therefore, suggests that endogenous progesterone is pro bably responsible for previously observed increase in B-max during the luteal phase of the female menstrual cycle. These findings may sugges t possible therapeutic strategies for modulation of beta(2)-AR in prem enstrual asthma.