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A specific antiserum to rat GH (anti-rGH) raised in sheep was used in young male and lactating rats. In both models a group of rats was found which appeared to generate a low response (low responders) to the injected sheep immunoglobulin, and was characterized by the ability of the antiserum to cause inhibition of growth for more than 21 days in the male rats, and to abolish milk yield when prolactin concentrations were lowered in the females. In the groups which generated a high response to the anti-rGH (high responders), growth was retarded for only 2–3 days in male rats, with a moderate milk yield maintained in lactating animals.

The low-response animals were found to have a significantly longer half-life for circulating anti-rGH, when compared with the high-response animals. After 21 days, in the age-matched male rats, levels of anti-rGH were undetectable in the high-responders, whereas the low-response animals, which were nearly 160 g lighter, still had approximately 4·5 ml anti-rGH/1 in their circulation. This anti-rGH was still capable of neutralizing GH, as concentrations of insulin-like growth factor-I (IGF-I) were 13·6±3·5 (mean ± S.E.M.) and 76·9±2·0 nmol/l in the low-response and high-response groups respectively. The reason for these differences would appear to be that the immune response mounted by these low-response animals to the exogenous sheep immunoglobulin (i.e. rat anti-sheep) 7 days after treatment was less than 10% of that seen in the high-response group.

In male animals the concentration of IGF-I was positively correlated with growth rate.

It is concluded that the effectivenes of the anti-rGH was related to its clearance rate which in turn depended on the ability of the animal to mount an effective anti-sheep response.

Journal of Endocrinology (1991) 128, 229–237