No abstract

We found previously that porcine growth hormone (pGH) causes an increase in growth rate with a concurrent improvement in carcass composition in pigs. The somatomedin, insulin-like growth factor 1 (IGF-1), is though to play a major role in mediating some of the anabolic actions of GH, while the glucocorticoid hormones are potential counter-regulators of these effects. The present study was conducted to determine the temporal and dose-response relationship between GH administration and serum IGF-1 and cortisol concentrations in pigs. Twelve Yorkshire barrows, fitted with femoral artery catheters, were injected (im) with either 0, 10, 100 or 1,000 micrograms/kg pGH. Blood sampling began 40 min prior to pGH injection and was continued for 37 h. Serum GH, IGF-1 and cortisol concentrations were determined by radioimmunoassay. In control animals, serum GH concentrations ranged from 1.6 to 5.7 ng/ml over 37 h. In the animals treated with increasing doses of pGH, peak serum GH concentrations reached 28, 112 and 286 ng/ml and levels remained elevated for 4, 12 and 24 h, respectively. Serum IGF-1 concentrations were elevated by pGH after a lag time of 4 to 6 h. When the IGF-1 concentrations were integrated over time, the response appeared to be dose-dependent, with an ED50 of 710 micrograms/kg body weight (BW). Data for serum cortisol concentrations showed a great deal of individual variation. A transient increase in cortisol was observed, but only in the group treated with 1,000 micrograms pGH/kg BW. Cortisol levels returned to baseline 2 h after pGH injection.(ABSTRACT TRUNCATED AT 250 WORDS)

The morpholine compound BRL-47672 has a chemical structure similar to that of clenbuterol and causes similar anabolic effects in rats but has no actions on beta 2-adrenoceptors in vitro. It has been argued therefore that beta 2-adrenoceptors do not mediate the anabolic effects of this family of compounds. In the present study BRL-47672 was shown to bind to rat beta 2-adrenoceptors with low affinity (dissociation constant 16 microM) relative to clenbuterol (48 nM) and to be a very weak activator of adenylyl cyclase activity in rat skeletal muscle membranes in vitro. In contrast, acute administration of the drug to anesthetized rats in vivo caused an increase in muscle adenosine 3',5'-cyclic monophosphate output, and chronic treatment of conscious rats for > 6 days caused a significant increase in weight gain (69%) accounted for by increased muscle growth. The anabolic effects of BRL-47672 were not counteracted by daily injections of the drug ICI-118551 (2 mg/day) but were prevented when the same beta 2-antagonist was administered in the diet (200 mg/kg feed, equivalent to 4.3 mg/day). The beta 1-adrenoceptor selective antagonist CGP-20712A fed in the diet (200 mg/kg feed) failed to attenuate the response to BRL-47672. These results support the conclusion that BRL-47672 has little direct action on beta 2-adrenoceptors but suggest that the compound is metabolized rapidly in vivo to a potent beta 2-agonist. Thus the stimulation of muscle growth by BRL-47672 is via beta 2-adrenoceptors, with no contribution to this response from beta 1- or beta 3-adrenoceptor activation.

This study compared the anabolic effects of clenbuterol in male and female rats and determined the relative contribution of testicular and ovarian hormones to any observed gender difference. Seventy-two 12-wk-old rats were used in a 2 x 2 x 2 factorial design in which animals were either male or female, entire or gonadectomized at 3 wk of age, and fed either a control diet or a diet containing 4 mg clenbuterol/kg feed for 8 days. Compared with entire male rats, entire females gained 64% less weight, had lighter carcasses (-36%) and gastrocnemius muscles (-62%), and had higher plasma concentrations of the catabolic hormone corticosterone (P < 0.05). Castration had a negative effect on growth in male rats, and ovariectomy had a positive effect in females, but there was still a gender difference in body weight between gonadectomized males and females, which amounted to 34% of the gender difference observed in intact rats. The density of beta 2-adrenoceptors in skeletal muscle was not different between males and females, nor was it affected by gonadectomy. Clenbuterol increased both weight gain and gastrocnemius muscle weight, with the latter response in entire and castrated male rats (+ 1.31 and + 1.17 g) being more than double that seen in entire and ovariectomized females (+ 0.58 and + 0.55 g). The downregulation response of beta 2-adrenoceptors in this muscle was remarkably consistent in all treated groups (-50% to -53%).(ABSTRACT TRUNCATED AT 250 WORDS)

Guanfacine is an alpha 2-adrenoceptor agonist with antithermogenic properties. A single treatment of guanfacine caused a dose-related reduction in metabolic rate. The maximum reduction was 40%, and a dose of .5 mg/kg was close to that required to produce half this effect. It was determined whether the antithermogenic action of guanfacine would result in increased growth rate in mice. In animals treated once daily for 10 d (0, .125, .5, or 2 mg/kg), the drug caused dose-related reductions in feed intake, weight gain, and feed conversion efficiency. In a further experiment, mice were fed a restricted quantity of feed and treated for 14 d with guanfacine (.5 mg/kg twice daily). Because of repeated dosing, the antithermogenic effect of the drug was attenuated, so that metabolic rate was not lower in treated mice at the end of the experiment. Control and treated mice ate all the feed offered, but the guanfacine-treated group gained 2.9 g less weight (P < .01) than the controls. Half this difference in BW was accounted for by body water (P < .1), whereas body energy content was also reduced by the drug (P < .05). In a final experiment we sought possible sources of energy loss. Mice were treated with guanfacine (.5 mg/kg) three times over 24 h. Severe glucosuria was observed in the guanfacine-treated mice, with a tendency also toward increased output of fecal energy. We have confirmed that guanfacine has a powerful, if short-term, antithermogenic action. However, in mice, other effects of the drug on energy metabolism result in weight loss rather than growth stimulation.