Liver. Pancreas. Blood and vascular system. Adrenals. Excretion of water and electrolytes. Thymus.

The Liver

(a) Weight. Korenchevsky and his colleagues (Korenchevsky & Dennison, 1934; Korenchevsky, Hall & Ross, 1939) reported a decrease in the weight of the castrated rat's liver under the influence of oestrogen; this result was less obvious in non-castrated rats. Selye (19406) noticed a reduction in the weight of the liver in rats which had been given oestradiol. Such an effect of oestrogen does not appear to be a pronounced or constant reaction. Griffiths, Marks & Young (1941) noted an increase in the weight of the liver in rats which had been treated with oestrogen.

(b) Histological changes in the bile ducts have been observed by Gardner, Allen & Smith (1941) in mice after the administration of oestrogen. The compounds used were oestradiol dipropionate or benzoate (16.6 to 50γ weekly), oestrone (250γ weekly) and stilboestrol (250γ weekly). This treatment caused the bile ducts to become thickened, rigid, white and somewhat nodular. The main duct was less affected towards the duodenal end. The cystic duct was thickened up to the neck of the gall-bladder. Microscopically the enlarged ducts showed an increase of the epithelial folds and of the glands, which sometimes reached as far as the serosa. The epithelium was hyperplastic and the ducts increased in extent.

Battaceano & Vasiliu (1936) say that when given to dogs oestrone causes at first a diminution in the volume of the liver which is followed by an increase. In a dog with a biliary fistula doses ranging from 1,000 to 5,000 r.u. arrested the flow of bile.

(c) Hepatoma and haemangioma. Miller & Pybus (1941) have noted a high incidence of hepatoma and haemangioma among mice of the- CBA strain after their continued subjection to oestrogen. These tumours appeared in 44.4 per cent of the normal males in a group of mice which had received subcutaneous injections of 300 i.u. of oestrone in olive oil once a week. In castrated males treated in the same way hepatomas appeared in 6.5 per cent, but none of these tumours developed in normal females under similar conditions. Gorer (1940) states that among his CBA mice which lived 11 months or longer hepatomata appeared in 18 of 35 males (51 per cent) and in 10 of 43 females (23 per cent).

Ovary, testis. Freemartins. Accessory generative organs.

Ovary, Testis. Freemartins

MANY years before any androgenic compound was identified and made available in pure form for experiment much had been learned about the biological properties of these hormones by noting the results of castration, transplantation of testes or the injection of testicular extracts. A study of the conditions in which freemartins were produced supplied additional knowledge, and inquiries into the changes in the gonads and accessory genital organs of animals which have a limited breeding season also gave valuable information. Later work with the pure hormones has confirmed and extended the knowledge thus acquired.

Permanent and transient effects. Some of the effects of androgen on the reproductive organs are permanent, others are reversible and endure only while androgen is being supplied in adequate quantity. The permanent effects are produced when growth and sexual development are still incomplete. This does not mean that lasting changes can be brought about only during embryological life, for many organs do not acquire their permanent form and character until long after birth. The gonads become fully differentiated early in embryological existence and afterwards remain relatively immune from permanent injury by androgen. The accessory generative organs complete their development much later and meanwhile their growth and form may be permanently interfered with by androgen. For example, the larynx and the bony pelvis do not acquire their ultimate masculine or feminine conformations until puberty and after; earlier in life they may become permanently deformed under androgenic influence. A few structures, of which the clitoris is an example, appear to remain, even in the adult, susceptible to some degree of permanent metamorphosis when submitted to an excess of androgen, and this seems true also of the facial dermis; for a beard once grown is slow to disappear after the chief sources of androgen have been removed.

Age. Afferent nervous stimuli. Changes of external temperature. Seasons. Oestrous cycle. Pregnancy. Gonadectomy. Partial gonadectomy, cryptorchidism and sterilization by X-rays. Gonadal hormones. Gonadotrophins. Sex. Nutrition.

THE pituitary by its power to supply trophins to the gonads is the mainspring of reproductive activity, and it may be of interest to consider some of the circumstances which affect this gonadotrophic function.

Age

The pituitary may produce some gonadotrophin at an early stage of existence. Smith & Dortzbach (1929) implanted pituitaries from foetal pigs into immature female mice. With the pituitaries of foetal pigs having a crown-rump length of 14 to 15 cm., no response was obtained; those from embryos measuring 18 cm. or more gave a positive result, namely follicular maturation, distension of the uterus and opening of the vagina. The gonadotrophic content of the foetal pig's pituitary, as indicated by these experiments, increased rapidly after the foetus had attained a length of 20 cm.

Hellbaum (1935) made comparative tests of the gonadotrophic potencies of pituitaries taken from foetal, immature and adult horses, and from mares and geldings. Positive tests were given by the pituitaries of foetal and immature horses, though the effect was less than that produced by the pituitaries of adults when given in equal quantity. Smith & Engle (1927) showed that infantile rats between 5 and 30 days after birth produced some gonadotrophin, for their pituitaries, when implanted into 17-day-old mice at the rate of two to six pituitaries daily, caused opening of the vagina and other signs of precocious maturity; and Clark (1935) by similar methods found that a sharp rise in the gonadotrophic potency of the rat's pituitary occurred between the 13th and 20th day of postnatal life. Wolfe & Cleveland (1931) tested the capacity of anterior pituitary extracts prepared from immature and mature rabbits to induce ovulation in sexually mature rabbits. The extracts were injected into the marginal ear vein of the test animal, whose ovaries were examined 24 hours later. Using amounts of extract which represented equal weights of pituitary gland, they found that the pituitaries of rabbits aged from 10 to 14 weeks were as potent, or nearly so, as those of adults. On the other hand the pituitaries of rabbits 4 or 5 weeks old, given in comparable doses, always failed to cause ovulation.

Introductory remarks. General review of biological action. Gradients of influence. Sources, inactivation and excretion.

Introductory Remarks

THE term androgen is used here as a collective title for compounds which resemble testosterone in biological action. The chief function of these hormones is to stimulate the development and activity of the accessory male reproductive organs. On the general dimensions of the body androgens have little effect, the smaller size of the female in mankind and in many other mammals being due to the action of oestrogen rather than to a deficiency of androgen. On the skeleton and general conformation of the body the androgens appear to exercise some influence, as seen, for example, in pathological cases of virilism in women, a condition which is accompanied by an excessive excretion of androgen in the urine. When this disease affects young girls the shape of the body tends in time to become masculine in character; whereas with defective gonadal development in young males the contours of the body may become distinctly feminine, the hips being broad compared with the shoulders. The falsetto voice and hairless face of the eunuch who has been castrated in childhood may be attributed also to a deficiency of androgen; for the testis is the chief though not the only source of this kind of hormone. The distribution of hair on the body in men, the extent of the facial sinuses, and the many curious sexual adornments and peculiarities which the males of different species acquire, especially in the mating and breeding season, also depend for their appearance and maintenance on an adequate supply of androgen. The crest of the newt, the cock's comb, the rugose and swollen clasping digits of the male frog, and the bright coloration of some fishes in the breeding season are examples. At present it will be unnecessary to discuss these curiosities at length, and attention will be concentrated on the more constant and vital activities of the androgens in mammals, including man.