title: Differential effects of dexamethasone and clenbuterol on rat growth and on beta2-adrenoceptors in lung and skeletal muscle.
abstract: Beta-adrenergic agonists increase growth rate, but their efficacy is reduced over time as the number of beta2-adrenoceptors in muscle decreases. Dexamethasone increases beta2-adrenoceptor density in many tissues, but this effect has not been reported in skeletal muscle. In this study, male rats were treated daily for 10 d with either clenbuterol (4 mg/kg of feed), dexamethasone (.2 mg/kg BW, s.c.), or clenbuterol plus dexamethasone. Untreated rats served as controls. Dexamethasone caused a marked suppression of growth rate, which resulted in decreased (P < .001) body weight (-29%), carcass weight (-30%), hind-limb muscles (-22%), omental fat (-22%), and heart weight (-10%). Feed intake was reduced (-26%), but feed conversion efficiency was also impaired (P < .001). Clenbuterol caused a small increase in growth rate (+6%; P < .05), with an increase in leg muscle (+7%; P < .01) and heart mass (+8%; P < .05). Feed efficiency was improved (P < .001) by clenbuterol. Rats given the combined treatment still showed a reduction in growth rate (-81%). Clenbuterol caused only a mild attenuation of the effects of dexamethasone on feed intake, BW, and carcass weight, but reduced the catabolic effect of dexamethasone on hind-limb muscle to only -8%. Clenbuterol caused a slight increase in the affinity beta2-adrenoceptors in lung for binding to the radioligand (-)[125I]iodocyanopindolol. Relative to control values, the density of beta2-adrenoceptors in lung was +31% with dexamethasone treatment, -45% with clenbuterol, and -23% with the combined treatment. Clenbuterol also decreased beta2-adrenoceptors in skeletal muscle (-35%), but so did dexamethasone (-13%), so the effects of the beta-adrenergic agonist were not attenuated through use of the combined treatment (-40%). The results show that the inductive effect of glucocorticoids on beta2-adrenoceptors is tissue-specific and that glucocorticoid treatment is not a useful adjunct to beta-adrenergic agonist treatment in animal production.
authors.affiliation: Central Queensland University, Department of Primary Industries, Queensland, Rockhampton, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Huang
authors.forename: C
authors.initials: C
authors.lastname: Gazzola
authors.forename: G G
authors.initials: GG
authors.lastname: Pegg
authors.forename: M N
authors.initials: MN
authors.lastname: Sillence
mesh_terms: D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000818:Animals; D001823:Body Composition; D002976:Clenbuterol / Q000008:administration & dosage / Q000494:pharmacology*; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D015536:Down-Regulation; D004357:Drug Synergism; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D020120:Iodocyanopindolol / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar / Q000254:growth & development*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D005938:Glucocorticoids; D018343:Receptors, Adrenergic, beta-2; D003907:Dexamethasone; D020120:Iodocyanopindolol; D002976:Clenbuterol