I. The activation of testosterone by the addition of organic acids. IT is well known that in the rat test testosterone exhibits a greater activity than androsterone, especially on the seminal vesicles of castrated rats. As we have recently shown [1936, 1, 2] this only applies to oily solutions of testosterone; testosterone is, strangely enough, hardly active when dissolved in paraffin oil or in aqueous solutions of glycerol. We found, however, that after the addition of certain carboxylic acids, especially of the fatty acid series such as ricinoleic acid, the activity reappeared. The effect of solutions in fatty oils, like sesame oil, is increased to a considerable degree by such saturated and unsaturated fatty acids. Meanwhile the number of the acids investigated has been considerably augmented and the earlier particulars supplemented. The weights of the seminal vesicles, prostate, Cowper's glands and preputial glands attained after administration of testosterone in combination with the new acids tested and with those of which the examination has been extended are given in Table I. Technique. The rats weighed 60-80 g. at the time of castration; the experiments were not made until 25-30 days after castration. The animals received once a day a dose of 50y testosterone during 10 days, subcutaneously injected together with the quantity of acid mentioned dissolved in 0 5 ml. sesame oil. The rats were killed on the 11th day and the accessory organs were weighed immediately. Fatty acids which are solid at room temperature, e.g. hydroxyacids and stearic acid, frequently had to be dissolved and injected at body temperature on account of their low solubility. The acids are arranged in the table approximately according to decreasing activity. Some of them, e.g. suberic, mandelic, tropic, nicotinic, piperic and oc-naphthoic acids, are only very slightly soluble and for this reason their solutions were almost inactive; thus the question whether the acids themselves are active or not was left open. Some proved to be toxic or produced pronounced local irritation, e.g. glycerophosphoric, undecylenic, phenylpropiolic, tetrolic, phenylacetic, lactic, pyruvic, acetic and formic acids, with which therefore the values obtained varied considerably. The irritating effect of the latter acids is probably due to their high acidity. Saturated higher fatty acids such as palmitic acid produce practically no irritation. As will easily be seen from Fig. 1 the increase of activity can attain a considerable value with increasing doses of the acid. Still higher doses generally caused technical difficulties due to the saturation limit being attained or to (1970)
