Nm. Wheeldon et al., INFLUENCE OF SEX-STEROID HORMONES ON THE REGULATION OF LYMPHOCYTE BETA(2)-ADRENOCEPTORS DURING THE MENSTRUAL-CYCLE, British journal of clinical pharmacology, 37(6), 1994, pp. 583-588
1 Up to 40% of female asthmatic subjects suffer a premenstrual deterio
ration in their condition which may be ameliorated by progesterone sup
plementation, although the mechanism responsible for this phenomenon i
s 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 stu
dy was to determine whether cyclical alterations in beta(2)-adrenocept
or expression, occurring under the influence of ovarian sex-steroid ho
rmones, may offer an explanation for these findings. In vitro, paramet
ers of lymphocyte beta(2)-adrenoceptor function were investigated in n
ine 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 con
trols studied at the same time intervals. 3 In female subjects there w
ere significant increases in serum concentrations of oestradiol (3.3-f
old) and progesterone (10.6-fold) between the follicular and luteal ph
ases 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 densit
y (B-max) and in maximal cyclic AMP response to isoprenaline (E(max)),
which were significantly higher than in male subjects. Mean differenc
es (95% CI) between male and female subjects on visit 2 were 1.09 (0.4
9 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 unch
anged 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 o
bserved gender differences of in vivo beta(2)-responses. Furthermore,
the rapid hormone flux and fall in beta(2)-adrenoceptor density and cy
clic AMP response between luteal and follicular phases may also provid
e a possible mechanism for premenstrual deterioration in asthma and it
s response to progesterone.