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 (Bmax) and in maximal cyclic AMP response to isoprenaline (Emax), 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 Bmax, and 3.42 (0.80 to 6.04) pmol/10(6) cells (P = 0.02) for Emax.(ABSTRACT TRUNCATED AT 250 WORDS)
Wheeldon
N M
NM
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, Scotland.
Newnham
D M
DM
Coutie
W J
WJ
Peters
J A
JA
McDevitt
D G
DG
Lipworth
B J
BJ
D000328:Adult; D000704:Analysis of Variance; D000242:Cyclic AMP / Q000096:biosynthesis; D004958:Estradiol / Q000097:blood; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008597:Menstrual Cycle / Q000097:blood*; D011374:Progesterone / Q000097:blood; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D012016:Reference Values; D012727:Sex Characteristics
D012739:Gonadal Steroid Hormones; D018343:Receptors, Adrenergic, beta-2; D011374:Progesterone; D004958:Estradiol; D000242:Cyclic AMP