Tan K S, McFarlane L C, Coutie W J, Lipworth B J
Department of Clinical Pharmacology, University of Dundee, Ninewells Hospital, UK.
Br J Clin Pharmacol. 1996 May;41(5):414-6. doi: 10.1046/j.1365-2125.1996.3311.x.
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 micrograms or medroxyprogesterone 10 mg in a cross-over study. Lymphocyte beta 2-AR parameters were evaluated at baseline (t0), 24 h (t24) and 72 h (t72) after ingestion. Baseline levels of progesterone and oestradiol were comparable on both cycles. Receptor density (Bmax) increased significantly (P < 0.01) from t0 after progesterone but not oestradiol at t 4: a 1.39-fold geometric mean difference (95% CI 0.96-2.00) between t24 vs t0. Receptor affinity (kd) and maximal cAMP response to isoprenaline (Emax) 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 Bmax 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.
我们之前已经表明,淋巴细胞β2 - 肾上腺素能受体(AR)受性甾体激素的周期性调控,在月经周期的黄体期受体密度更高。也有人推测,β2 - AR的异常周期性调节可能是经前哮喘的一种潜在机制。我们对8名正常健康女性研究了外源性雌性甾体激素对淋巴细胞β2 - AR功能的影响。在两个连续的月经周期的卵泡期(第1 - 6天)对她们进行评估。在一项交叉研究中,她们被随机分为单次口服50微克乙炔雌二醇或10毫克甲羟孕酮。在摄入药物后的基线(t0)、24小时(t24)和72小时(t72)评估淋巴细胞β2 - AR参数。两个周期的孕酮和雌二醇基线水平相当。孕酮给药后,受体密度(Bmax)从t0开始显著增加(P < 0.01),但雌二醇给药后在t24时未增加:t24与t0之间的几何平均差异为1.39倍(95% CI 0.96 - 2.00)。两种治疗均未改变受体亲和力(kd)和对异丙肾上腺素的最大cAMP反应(Emax)。这些结果表明,在卵泡期给予外源性孕酮而非雌二醇,可显著增加β2 - AR。因此,这表明内源性孕酮可能是之前观察到的女性月经周期黄体期Bmax增加的原因。这些发现可能为经前哮喘中β2 - AR的调节提供可能的治疗策略。