Quantitative Study of the Effects of Implanting Tablets of Oestrogens and Androgens in Rats

Abstract

The prolonged administration of oestrogenic substances to male animals produces very marked effects. The more interesting of these effects, notably those on growth and on the gonads, are apparently exerted indirectly by depression of hypophyseal activity. Much of the work has been carried out on the male rat, in which stunting of the body and atrophy of the testes can readily be obtained by prolonged administration of oestrogens. This capacity to depress pituitary activity is seen both in the naturally-occurring oestrogens and in the synthetic oestrogens such as diethylstilboestrol [Noble, 1939].It is already known that substances which have multiple properties in common may not show them equally intensely. As an extreme example it may be recalled that methyl testosterone is highly androgenic and slightly progestational, while progesterone is highly progestational and faintly androgenic. Also, evidence is already appearing that the various multiple activities of the oestrogens are not equally intense in all oestro¬ genic substances. Thus, the theoretical possibility exists that further work will result in the preparation of substances which, for instance, depress pituitary activity but do not cause the characteristic changes in the reproductive tract of the female, or again, of substances which depress only one pituitary function. Such substances might be of great practical as well as theoretical interest, since the use of existing oestrogens to correct an overactivity of the pituitary gland (overgrowth, for instance) would lead to unwanted hyperplasia in the reproductive tract.Detailed comparison of different substances can only be made by accu¬ rately assaying all their known activities, and it is important that a full range of appropriate methods should be available. Accurate methods have already been worked out for many of the activities, but quantitative study of the antigrowth and antigonad effect has not yet progressed far. Both of these are essentially long-term effects and it has already been shown that administration of the substances by the tablet implantation technique produces the result effectively and with the minimum of labour [Deanesly, 1939]. The present paper provides a quantitative basis for the simple comparison of the antipituitary activity of oestrogenic substances. Kk