SYNERGISM OF TESTOSTERONE PROPIONATE WITH GROWTH-HORMONE IN PROMOTING GROWTH OF HYPOPHYSECTOMIZED RATS - EFFECT OF SEXUAL-DIFFERENTIATION

The effect of testosterone propionate (TP), alone and in combination with porcine GH, on the growth of hypophysectomized rats was investigated. An initial study determined doses of TP and GH which would result in a synergistic response. Hypophysectomized male rats, approximately 40 days of age, received GH at doses of 5, 25 and 62.5 μg/day administered in two injections/day at 08.00 and 16.00 h. At all doses of GH, administration of TP at 100 μg/day significantly enhanced the GH-stimulated rate of growth. This growth enhancement by TP was greatest in combination with GH at 25 μg/day. In a subsequent study, growth responses to 25 μg GH/day and 100 μg TP/day were examined in animals with differing degrees of sexual differentiation. Sex groups were: intact males, males castrated at 11 days of age and females administered 100 μg TP at 3 days of age (masculinized rats), and males castrated at 2 days of age and normal females (non-masculinized rats). In all sex groups, growth of hypophysectomized rats was stimulated by GH. Genetic sex and masculinization did not influence the response to GH. Masculinized hypophysectomized rats exhibited significantly greater rates of growth and final live, empty body, liver and kidney weights than non-masculinized hypophysectomized rats. All sex groups other than normal females responded synergistically to the combination treatment of GH plus TP. Rats that experienced neonatal exposure to testosterone became programmed to respond to testosterone and demonstrated greater rates of growth and body and organ weights when administered the combination of GH plus TP. These data indicate that TP synergizes with GH to promote growth of hypophysectomized rats appropriately programmed to respond. The ability to manifest a synergistic response is a differentiated trait dependent upon exposure to testosterone during the appropriate period of development. The time of differentiation of this ability to respond to testosterone occurs earlier than that for differentiation of body growth.