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 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.
Tan
K S
KS
Department of Clinical Pharmacology, University of Dundee, Ninewells Hospital, UK.
McFarlane
L C
LC
Coutie
W J
WJ
Lipworth
B J
BJ
D000328:Adult; D018592:Cross-Over Studies; D045166:Estradiol Congeners / Q000494:pharmacology*; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008183:Luteal Phase / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects*; D008525:Medroxyprogesterone / Q000494:pharmacology*; D045167:Progesterone Congeners / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism
D045166:Estradiol Congeners; D045167:Progesterone Congeners; D011943:Receptors, Adrenergic, beta; D004997:Ethinyl Estradiol; D008525:Medroxyprogesterone