The activation of the male sex hormones. I

Abstract

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)

The Physiology of Pregnancy in the Rat. The Combined Action of Male and Female Hormones (Testosterone Propionate and Œstrone)

“…Since the action of testosterone propionate is a delayed one (Miescher, Wettstein and Tschopp [1936], Parkes [1936]), it was decided to examine the effect of two injections in 12 hours, and to test these against a slightly larger amount of cestrone. It was found that when '294 Hain …”

Multiple Activities of Androgenic Compounds

“…From these figures it would seem that 20 mg. of testosterone produces a response of the same order as 2 y of cestrone, and 20 mg. trans-dehydroandrosterone or andro-stenedione one similar to 10 y cestrone. Other experiments with these compounds, carried out with 3 injections on alternate days, suggest that under these conditions the addition of palmitic acid to the solution leads to an increase in the effectiveness of the dose, but to a lesser extent than is found in rats [Miescher, Tschopp, and Wettstein, 1936]. The most cestrogenic of the compounds, therefore, seems to be about one two-thousandth as active as cestrone.…”

“…In this respect, therefore, these two male hormone substances may be considered to have certain properties akin to those of progesterone but also others differing from them. The apparent capacity of testosterone to inhibit the cestrous cycle changes in the vagina of the adult female rat [Robson, 1936;Miescher and Tschopp, 1936] may also depend on its power to modify the action of cestrone in the direction of mucification. Selye, McEuen, and Collip [1936] have described stimulation of the mammary glands of the gonadectomised rat by administration of testosterone, while Wells and Moore [1936] have stated that spermatogenesis may be initiated in the quiescent ground squirrel by injection of testosterone.…”

The progesterone-like action of testosterone and certain related compounds

“…The compounds were dissolved in arachis oil, and injected sub cutaneously. At the time these experiments were being carried out, it was demonstrated by Miescher, Wettstein, and Tschopp (1936) that the activity of testosterone could be much increased by adding fatty acids to the oil solution, a result almost certainly brought about by retardation of absorption. In certain cases, therefore, a total of 1 gm.…”