No abstract

prepared this compound artificially. The natural and artificial preparations were similar in all respects, one capon unit being contained in about 10y and the effect on the seminal vesicles of castrated rats being greater than that on the prostate. According to Tschopp [1935; Ruzicka and Wettstein, 1935, p. 1270] 10y of testosterone injected into castrated rats for 10 days brought about an increase in the size of the seminal vesicles of about 300 % and of the prostate of about 113 %.. Laqueur et al. foumd that the effect of testosterone on the seminal vesicles and prostate of castrated rats could be doubled or even more than doubled, if a physiologically indifferent, impure extract, prepared from the tissues of

] we have shown that the male sexual hormone testosterone and its ester, testosterone propionate, have a powerful effect on the organs of ovariectomized rats. In the present paper the effect of testosterone propionate on normal female rats is described. Technique The technique used was the same as that in our previous papers. Artificial testosterone propionate was prepared and supplied by Messrs Ciba Ltd. Large doses of 05 and 1F5 mg. daily were chosen in order to overcome the effect of any antagonistic hormones which might be present in the female organism. The experiment was performed on 16 rats belonging to 3 litters. The rats were divided in such a way that litter-mates were present in each of the 3 groups. The average final age of the rats was 98 days and the hormone was injected daily for 21 days. The weights of the organs are summarized in Table I. In order to economize space the weights per unit of body weight are not given, but, as in our previous papers, where the conclusions based on these differ from those obtained from the actual weights, this is mentioned in the text. The detailed histological results will be published elsewhere.

A DETAILED investigation of the effect of cestrone * administered alone or simultaneously with testicular hormone is important (1) because the testes secrete both these hormones and (2) because pathological changes have been described in some of the organs of male rats after the administration of aestrone. Moore and Price (1932) by injecting aestronc into male rats obtaincd n marked decrease in the size of the testes, seminal vesicles nnd prostate. Simultaneous injection of testicular hormone prevented atrophy of the secondary sex organs but not of the testes. Lacassagno (1933), on injecting mice with oestrone for the lengthy pcriod of three months or mom, produced atrophy of the seminal vesicles but. a pathological onlargement of the posterior lobe of the prostate wit.h hyper-and mctaplasia of the epithelium, which showed in several places strat,Xcation and keratinisation. The histological picturo was rcminiscent of " epitheliome pavimenteaux cpidermoidc." Freud (1933) and David, Freud and De Jongh (1934). by injecting mstrone into male castrated rats, promoted the development of smooth muscle in the seminal vesicles and the enlargement of the ducts and lateral lobes of tho prostate with stratification of the duct epithelium. Simultaneous injection of tcsticular hormone prevented the changes due to cestrone, but increascd the effect of testicular hormone alone on the seminal vesicles. Burrows and Kennaway (1934) painted the skin of malo mice with a solution of estrone in benzene for 6 to 22 weeks, causing scrota1 hernia, atrophy of the testes and seminal vesicles and enlargemcnt of the anterior and dorsal lobes of the prostate. Histologically tho prostate showed conversion of the single layer of glandular celLs lining the alveoli into str8tXed epithelium, with subsequent kerntinisation of some layers and distension of tho alveoli by masses of keratin. Suppuration of the contents occurred in some of the alveoli. In tho prostatic tissue adjacent t,o the urethra a pronounced metaplasia of specid typo was observed : t.ho glandular parenchyma, consiyting in this region of ducts and alveoli lined by cubical or columnar cells, was convcrt.ed into solid cylinders of stratified In 1933 (Nature, vol. cxrxii. p. 205) tho English workers on female sex hormones agreed to give the name " oestrone " to the hormone variously desiCfnated I ' follicular hormone," " theelin," " ketohydroxyceRtrin," " ocstrin or " menformon." ~- 323

MIESCHER et at. [1936, 1, 2] found that the activity of testosterone on male sexual organs was greatly increased by esterification. Of the various esters prepared the propionate, as judged by short-duration experiments, proved to be the most effective. It brought about a greater increase in the size of the male sexual organs in castrated rats and also a longer duration of the effect than was obtained with other esters; e.g. after a single injection of 2 mg. of testosterone propionate, dissolved in 2 ml. of sesame oil, or after two injections of 1 mg. in 1 ml. of sesame oil with a 5-day interval, the maximum effect was obtained on about the 11th day after the first injection, the activity lasting at least 2-4 weeks. With testosterone the activity had disappeared by the 11th day, the maximum effect being observed a few days after the injection. Parkes [1936] also confirmed the results quoted above in short-duration experiments on the prostate and seminal vesicles. Such properties of the propionate would be important from a therapeutic viewpoint and it is also possible that testosterone is normally present in the body as an ester. On the basis of the experiments with the esters of testosterone Miescher et al. [1936, 2] confirmed the conclusion which we have repeatedly emphasized in our