Eur J Clin Pharmacol (1997) 52: 281±283
PHARMACODYNAMICS
K. S. Tan á L. C. McFarlane á B. J. Lipworth
Effect of exogenous female sex-steroid hormones on b2-adrenoceptors
in healthy males
Received: 22 October 1996 / Accepted in revised form: 17 January 1997
Abstract Objective: We have previously demonstrated
that exogenous progesterone, but not oestrogen, up-
regulated lymphocyte b2-adrenoceptors (b2-AR) when
given during the follicular phase in healthy females. In
the present study, we were interested to see whether this
facilitatory e€ect of female sex-steroid hormones could
be demonstrated in healthy males.
Methods: Nine healthy male volunteers with a mean age
of 24 years completed this randomised, double-blind,
placebo-controlled, cross-over study. They were ran-
domised to receive either oral placebo, oestradiol vale-
rate (4 mg) or medroxyprogesterone (40 mg). The study
medication was given in two divided doses 12 h apart.
Subjects attended the laboratory at baseline (T0 is
baseline), 1 h after ingestion of the second dose of study
medication (T1) and 24 h later (T24). At each visit, 60 ml
of peripheral blood was withdrawn for measurement of
serum oestradiol, progesterone and testosterone levels,
and for lymphocyte b2-AR parameters; density (Bmax),
binding anity (Kd) and maximal cyclic AMP response
to isoprenaline (Emax).
Results: Baseline levels of sex-steroid hormones were
comparable for each of the treatment periods. Serum
oestradiol levels increased signi®cantly, twofold, 1 h af-
ter ingestion of oestradiol but there was no signi®cant
change in levels of serum progesterone and testosterone.
Lymphocyte b2-AR parameters following treatment with
oestradiol and progesterone did not change signi®cantly
from baseline and were not di€erent from placebo.
Conclusion: In contrast to previously reported e€ects in
women, female sex-steroid hormones did not appear to
have any signi®cant facilitatory e€ects on lymphocyte b2-
AR parameters when given exogenously to healthy
males. This lack of e€ect may be due either to the ab-
K.S. Tan á L.C. McFarlane á B.J. Lipworth (&)
Department of Clinical Pharmacology,
Ninewells Hospital & Medical School,
University of Dundee, Dundee DD1 9SY, UK
Tel. +44-1382-660111 ext. 2180; fax +44-1382-644972
Ó Springer-Verlag 1997
sence of receptors for female sex hormones in b2-AR or
to reduced ecacy of female hormone-receptor coupling
in male lymphocytes.
Key words Oestrogen, Steroid hormones; male, b2-
adrenoceptor, lymphocyte
Introduction
Female sex-steroid hormones have been shown to have
an in¯uential role in the regulation or modulation of b2-
adrenoceptor (b2-AR) function. In vitro studies have
demonstrated the potentiating e€ects of female sex-ste-
roid hormones on the bronchorelaxant [1] and vasore-
laxant [2] e€ect of catecholamines. In vivo studies have
shown that healthy female subjects exhibit enhanced
sensitivity for a variety of systemic b2-AR mediated re-
sponses [3, 4]. Gender di€erences in the chronotropic
e€ects of isoprenaline have also been observed. These
are independent of body weight and appear to represent
true di€erences in b-adrenergic sensitivity at the tissue
level [5]. More recently, we have shown that lymphocyte
b2-AR function in normal females is under the cyclical
in¯uence of ovarian sex steroids, with greater b2-AR
density and cyclic AMP response to isoprenaline during
the luteal phase than the follicular phase. These obser-
vations are associated with raised post-ovulatory levels
of progesterone and oestrogen [6]. In addition, we have
observed that the administration of exogenous proges-
terone, but not oestrogen, in healthy females during the
follicular phase produced up-regulation of lymphocyte
b2-AR density [7].
We were therefore interested to ®nd out whether this
e€ect of exogenous female sex-steroid hormones was
sex-speci®c and to see whether it is possible to `feminise'
male b2-AR. The aim of this study was to determine
whether exogenously administered female hormones,
oestrogen and progesterone, would have similar facili-
tatory e€ects on lymphocyte b2-AR in healthy males.