growth and metabolism have been
measured in efforts to identify indirect
mechanisms by which phenethanolamines
may influence growth and body composi-
tion. In sheep administered cimaterol,
increased growth hormone and T4, and
decreased insulin-like growth factor 1
(IGF-1) concentrations were observed after
6 weeks of treatment (Beermann et al.,
1987). In contrast, O’Connor et al.(1991b)
observed no change in IGF-1 and decreased
T4 concentrations after 3 weeks of
cimaterol treatment in sheep. Young et al.
(1995) also reported no significant change
in IGF-1 concentration following chronic
administration of clenbuterol in sheep. In
cattle treated with cimaterol, Chikhou et al.
(1991) reported an acute decrease in mean
growth hormone concentration, followed
by a chronic increase in growth hormone
and decrease in IGF-1 concentrations. Also
in steers treated with cimaterol, Dawson et
al.(1993) identified no significant differ-
ences in mean concentrations of growth
hormone or IGF-1. These authors also
observed an absence of regular growth
hormone secretion cycles in cattle treated
with cimaterol, suggesting that cimaterol
treatment may have disrupted the rhythm
of growth hormone secretion. In broilers
treated with clenbuterol, Buyse et al.
(1991) reported no consistent effects on
plasma thyroid hormone, growth hormone,
IGF-1 or corticosterone concentrations.
In general, the effects of phene-
thanolamines on hormone concentrations
have been insignificant or inconsistent
across studies, indicating that these
hormones are probably not important to
the mechanism of action of phenethano-
lamines. Further evidence that the effects
of phenethanolamines are not mediated
through the growth hormone axis is
provided by investigations of the effects of
phenethanolamines and growth hormone
administered in combination. Additive
effects of growth hormone with clenbuterol
in cattle (Maltin et al., 1990), salbutamol in
pigs (Hansen et al., 1997) and ractopamine
in pigs (Jones et al., 1989) were identified,
suggesting that the growth-promoting
effects of these compounds are mediatedby different mechanistic pathways.
Additionally, it has been shown recently
using direct hind-limb arterial infusion of
steers that increased muscle protein accre-
tion in response to cimaterol treatment is
due to direct actions on the muscle, rather
than indirect effects such as cardiovascular
activity, endocrine status or splanchnic
tissue metabolism (Byrem et al., 1998).Blood flowIncreased blood flow has been demon-
strated in cattle (Eisemann and
Huntington, 1993; Byrem et al., 1998),
sheep (Aurousseau et al., 1993) and pigs
(Mersmann, 1989) in response to
clenbuterol or cimaterol treatment. This
response may enhance the effects of
phenethanolamine treatment on skeletal
muscle and adipose tissue by delivering
increased amounts of substrate and
energy source to skeletal muscle for pro-
tein synthesis, and by carrying non-esteri-
fied fatty acids away from adipose tissue
to enhance lipid degradation (see
Mersmann, 1998).The -adrenergic family of receptorsAlthough the effects of phenethanolamines
on skeletal muscle have not yet been
linked directly to activation of -adrenergic
receptors, the possibility that these
receptors facilitate at least a portion of the
anabolic effects of phenethanolamines
cannot be eliminated. This, combined with
the importance of -adrenergic receptors in
the regulation of lipid metabolism, make
an understanding of the -adrenergic
family of receptors critical to discerning
the mechanism of action of phenethano-
lamines in livestock.
Endogenous agonists of the -adrenergic
receptors include norepinephrine, a neuro-
transmitter produced by the sympathetic
nervous system, and epinephrine, a circulat-
ing hormone produced by the adrenal
medulla. The -adrenergic receptors are
members of the membrane-bound, G-78 D.E. Moody et al.04 Farm Animal Metabolism 04 20/4/00 12:02 pm Page 78