INFLUENCE OF SEX-STEROID HORMONES ON THE REGULATION OF LYMPHOCYTE BETA(2)-ADRENOCEPTORS DURING THE MENSTRUAL-CYCLE

1 Up to 40% of female asthmatic subjects suffer a premenstrual deterioration in their condition which may be ameliorated by progesterone supplementation, although the mechanism responsible for this phenomenon is not understood. In vitro studies have shown that female sex-steroid hormones potentiate the bronchorelaxant effect of isoprenaline, whilst in vivo it has been shown that females exhibit greater sensitivity of systemic beta(2)-adrenoceptor responses. 2 The aim of the present study was to determine whether cyclical alterations in beta(2)-adrenoceptor expression, occurring under the influence of ovarian sex-steroid hormones, may offer an explanation for these findings. In vitro, parameters of lymphocyte beta(2)-adrenoceptor function were investigated in nine normal female subjects (aged 24 +/- 2 years) during the follicular (day 2-4) and luteal (day 21-23) phases of their menstrual cycle, and results were compared with those of nine age-matched healthy male controls studied at the same time intervals. 3 In female subjects there were significant increases in serum concentrations of oestradiol (3.3-fold) and progesterone (10.6-fold) between the follicular and luteal phases of the menstrual cycle, whereas no changes occurred in males. 4 In females during the luteal phase, the increase in sex-steroid hormones was mirrored by an increase in lymphocyte beta(2)-adrenoceptor density (B-max) and in maximal cyclic AMP response to isoprenaline (E(max)), which were significantly higher than in male subjects. Mean differences (95% CI) between male and female subjects on visit 2 were 1.09 (0.49 to 1.69) fmol/10(6) cells (P = 0.001) for B-max, and 3.42 (0.80 to 6.04) pmol/10(6) cells (P = 0.02) for Em,x. The mean difference (95% CI) in E(max) between visits 1 and 2 in females was 2.57 (0.32 to 4.82) pmol/10(6) cells (P = 0.03). The receptor affinity (K-d) remained unchanged in both sexes. 5 These findings suggest that lymphocyte beta(2)-adrenoceptors are regulated under the influence of ovarian sex-steroid hormones during the menstrual cycle, and may account for previously observed gender differences of in vivo beta(2)-responses. Furthermore, the rapid hormone flux and fall in beta(2)-adrenoceptor density and cyclic AMP response between luteal and follicular phases may also provide a possible mechanism for premenstrual deterioration in asthma and its response to progesterone.