The Suppressive Effects of Testosterone on Growth in Young Chickens Appears to be Mediated via a Peripheral Androgen Receptor; Studies of the Anti-Androgen ICI 176,334

Abstract

ICI 176,334 is a nonsteroidal anti-androgen that has been shown to selectively block peripheral androgen receptors in rats and is presumed to do so in chickens. In chickens, androgens stimulate secondary sexual characteristics (e.g., comb), but inhibit growth and the immune tissues. The present study examined the effect of dietary ICI 176,334 (5 or 25 mg/kg body weight) on growth in chickens in the presence or absence of testosterone treatment (as 1-cm long silastic implants). Treatments began at 2 wk of age and continued through 6 wk of age. Testosterone alone reduced body growth (average daily gain and shank-toe length, together with weights of the body, skeletal muscle, and the bursa of Fabricius, an immune tissue), and stimulated comb development. At the low dose (5 mg/kg), ICI 176,334 alone had no effect on body growth or organ weight with the exception that comb weight was reduced. At the high dose (25 mg/kg), ICI 176,334 decreased growth (body weight, average daily gain, and shank-toe length) and organ weights (breast muscle, bursa of Fabricius, testis, and comb weights). This effect may represent a toxicity. As might be expected with an anti-androgen, ICI 176,334 (at either 5 or 25 mg/kg) completely suppressed the stimulation of comb growth evoked by testosterone. Similarly, ICI 176,334 (5 mg/kg) overcame, albeit partially, the growth-suppressive effects of testosterone (on body weight, average daily gain, shank-toe length, and breast muscle weight) and also had inhibitory effects on the weights of the testis and bursa of Fabricius. The anti-androgen, ICI 176,334, did not influence the reduction in circulating concentrations of luteinizing hormone occurring after testosterone treatment. The present data are consistent with the growth-suppressive effects of testosterone in chickens being mediated via a peripheral androgen receptor. No effects of either testosterone or ICI 176,334 were observed on circulating concentrations of insulin-like growth factor-I despite the marked changes in growth rate.