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As previously reported [Reid, 1953a], ACTH preparations do not readily enhance the diabetogenic potency (in cats) of purified preparations of growth hormone (GH), in contrast to that of crude ox-pituitary extracts. It is now postulated that crude extracts are rich in a 'co-factor' which enables, or helps, ACTH to enhance the diabetogenic activity of GH. Some evidence has been found for the presence of such a 'co-factor' in crude chorionic gonadotrophin, in semipurified LH, and in crude 'albumin fractions' obtained as by-products in the isolation of GH from crude extracts.It was previously shown that the effectiveness of different ACTH preparations, in enhancing the diabetogenic potency of crude GH preparations, bore little relation to their activity in the Sayers test (ascorbic acid depletion). It now appears that this lack of correlation is not attributable to differences in the rate of absorption after injection into cats.The diabetogenic potency of an alkaline pituitary extract was found to be enhanced when a preparation of ox 'crude corticotropin' (containing some GH), or of pig GH, was given concurrently at an acidic pH so that its intrinsic diabetogenic activity was low. This ' ACTH-like activity' was not found with purified ox GH under these conditions.

The ratio of diabetogenic activity (in the cat) to growth-promoting activity (in the rat) of growth hormone (GH) preparations obtained by various purification procedures is constant within the limits of experimental error.Purified GH preparations were partially inactivated in a variety of ways, and the products assayed for diabetogenic and for growth-promoting activity. It appeared that the two activities were lost to the same degree.The biological activity of the GH molecule appears to depend on the integrity of the ε-amino groups (lysine), but not on that of the α-amino groups (alanine and phenylalanine).

During storage for 3 years in the dry state, the growth-promoting potency (in rats) of a crude pituitary extract or of purified preparations of growth hormone did not show any detectable change. Storage did not impair the diabetogenic potency (in cats) of the purified preparations, but may have impaired that of the crude extract.

1. Procedures are described for the approximate assessment, in the intact cat, of the diabetogenic potency of growth hormone preparations from ox anterior-pituitary glands (section A).2. Partially depancreatized rats (three strains) and alloxan-diabetic rats (two strains) were insufficiently sensitive to such preparations to be of use as test animals (section B).

Different batches of crude bovine pituitary extract were compared with respect to the 'D/G ratio', i.e. the ratio of diabetogenic activity in cats to growth-promoting activity in rats. The ratio was low for some extracts which had been incubated as in the experiments of Marks & Young [1940], but wide variations were found with 'normal' (non-incubated) extracts, for some of which the ratio was notably high.Purified preparations of the diabetogenic factor isolated from crude extracts appeared to consist predominantly of growth hormone (GH), as shown particularly by examination in the ultracentrifuge (see Addendum).The possibility that 'purified GH' might, in common with crude extracts, vary in D/G ratio, received little support from tests performed on semi-purified GH fractions isolated from crude extracts, or on purified GH preparations subjected to mildly destructive treatments such as incubation with carboxypeptidase, which did not impair either diabetogenic or growth-promoting activity. Tests with the GH preparation (pig) of Raben & Westermeyer [1952] did not confirm their claim that it lacks diabetogenic activity.The growth-promoting activity of GH is reduced by ACTH or posterior-pituitary extract, and enhanced by thyrotrophin. The diabetogenic activity of GH is known to be enhanced by ACTH under certain conditions. Variations among crude extracts in D/G ratio may thus be attributable to variations in the content of certain hormones other than GH.Data are presented for changes in body-weight in cats treated with crude pituitary extracts or purified GH.